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Volume 33,Issue 3,2026 Table of Contents
2026, 33(3):225-232.
DOI: 10.3872/j.issn.1007-385X.2026.03.001
Abstract:
[Abstract] Dendritic cells (DCs), as the core initiators and regulators of anti-tumor immune responses, have emerged as important targets in tumor immunotherapy. Immunotherapeutic strategies targeting DCs, such as DC vaccines, have shown unique advantages in anti-tumor treatment. However, several challenges remain, including insufficient antigen presentation efficiency, resistance from the immunosuppressive microenvironment, and difficulties in achieving specific functional modulation. DCs in the tumor microenvironment (TME) exhibit high heterogeneity, and different DC subpopulations show complex diversity in differentiation and development, immune regulation, and effector outcomes. Elucidating the precise phenotypes and functional mechanisms of DC subpopulations is therefore crucial for developing novel DC-targeted immunotherapeutic strategies. In the TME, recruited conventional DCs, plasmacytoid DCs, and monocyte-derived DCs can interact with tumor-infiltrating immune cells and non-immune cells within the TME (including tumor cells, fibroblasts, endothelial cells, etc.) to activate anti-tumor immune responses. However, the TME can suppress DC recruitment and antigen-presenting capabilities through various means, including transcriptional regulation, epigenetic regulation, and metabolic reprogramming, and may even induce their transformation into tolerogenic DCs. Notably, newly discovered mature DCs enriched with immunoregulatory molecules exhibit bidirectional immunoregulatory functions, yet their origins and immune regulatory networks require in-depth research. With the development of single-cell technology and spatial omics, researchers can systematically analyze the functional diversity of DC subpopulations and their spatiotemporal interactions with the TME at single-cell resolution. These approaches are expected to provide new targets and insights for the development of next-generation precision immunotherapeutic strategies.[Key words] tumor microenvironment; dendritic cell subset; tumor; immunotherapy; immune checkpoint blockade therapy; cell-cell communication
[Abstract] Dendritic cells (DCs), as the core initiators and regulators of anti-tumor immune responses, have emerged as important targets in tumor immunotherapy. Immunotherapeutic strategies targeting DCs, such as DC vaccines, have shown unique advantages in anti-tumor treatment. However, several challenges remain, including insufficient antigen presentation efficiency, resistance from the immunosuppressive microenvironment, and difficulties in achieving specific functional modulation. DCs in the tumor microenvironment (TME) exhibit high heterogeneity, and different DC subpopulations show complex diversity in differentiation and development, immune regulation, and effector outcomes. Elucidating the precise phenotypes and functional mechanisms of DC subpopulations is therefore crucial for developing novel DC-targeted immunotherapeutic strategies. In the TME, recruited conventional DCs, plasmacytoid DCs, and monocyte-derived DCs can interact with tumor-infiltrating immune cells and non-immune cells within the TME (including tumor cells, fibroblasts, endothelial cells, etc.) to activate anti-tumor immune responses. However, the TME can suppress DC recruitment and antigen-presenting capabilities through various means, including transcriptional regulation, epigenetic regulation, and metabolic reprogramming, and may even induce their transformation into tolerogenic DCs. Notably, newly discovered mature DCs enriched with immunoregulatory molecules exhibit bidirectional immunoregulatory functions, yet their origins and immune regulatory networks require in-depth research. With the development of single-cell technology and spatial omics, researchers can systematically analyze the functional diversity of DC subpopulations and their spatiotemporal interactions with the TME at single-cell resolution. These approaches are expected to provide new targets and insights for the development of next-generation precision immunotherapeutic strategies.[Key words] tumor microenvironment; dendritic cell subset; tumor; immunotherapy; immune checkpoint blockade therapy; cell-cell communication
YANG Jianxun
,
ZHENG Rui
,
LIANG Sixin
,
PAN Jie
,
LI Yanlong
,
ZHAI Chenxi
,
ZHAO Xiaojuan
,
WANG Pengju
,
DONG Hao
,
YAN Bo
,
SUN Zhihong
,
ANG Angang
2026, 33(3):233-242.
DOI: 10.3872/j.issn.1007-385X.2026.03.002
Abstract:
[Abstract] Objective: To investigate whether ectopic expression of hemoglobin subunits (HBA/HBB) improves chimeric antigen receptor T cell (CAR-T cell) function and enhances cytotoxicity against tumor cells under hypoxic conditions. Methods: The CAR sequence targeting HER2 was synthesized by full gene synthesis technology, and the CAR lentiviral vectors co-expressing HBA or HBB were constructed. After packaging the lentivirus, human primary T lymphocytes were infected to prepare HBA CAR-T and HBB CAR-T. Hypoxia in mouse solid tumors was detected by hypoxia probes. The proportion of CAR-T cells in the tumor, the percentage of CAR-T cells expressing hemoglobin, and the levels of reactive oxygen species and apoptosis of CAR-T cells under different conditions were detected by flow cytometry. The expression of related hemoglobin subunits in CAR-T cells was detected by WB assay. The proliferation level of cells was detected by hemocytometer, the cytotoxicity of CAR-T cells against tumor cells was detected by luciferase reporter assay, the expression level of HIF-1α in CAR-T cells was detected by qPCR, the oxygen content in T cells was detected by MitoXpress Intra kit. Results: The solid tumor models constructed from different cell lines all exhibited significant hypoxia, and the infiltration level of CAR-T cells was significantly negatively correlated with the degree of hypoxia (P < 0.000 1). HBA CAR-T and HBB CAR-T were successfully constructed (positive rate > 60%), and the corresponding hemoglobin subunits were stably expressed. Under hypoxic conditions, the ROS level and apoptosis level of HBA CAR-T and HBB CAR-T significantly decreased, and their proliferation and cytotoxicity against tumor cells were significantly stronger than those of conventional CAR-T cells (all P < 0.05). HBA CAR-T and HBB CAR-T showed decreased HIF-1α expression (all P < 0.001), and their level of hypoxia significantly decreased (all P < 0.001). Conclusion: The ectopic expression of hemoglobin can reverse the functional impairment of CAR-T cells under hypoxic conditions and enhance their cytotoxicity against tumor cells in vitro.
[Abstract] Objective: To investigate whether ectopic expression of hemoglobin subunits (HBA/HBB) improves chimeric antigen receptor T cell (CAR-T cell) function and enhances cytotoxicity against tumor cells under hypoxic conditions. Methods: The CAR sequence targeting HER2 was synthesized by full gene synthesis technology, and the CAR lentiviral vectors co-expressing HBA or HBB were constructed. After packaging the lentivirus, human primary T lymphocytes were infected to prepare HBA CAR-T and HBB CAR-T. Hypoxia in mouse solid tumors was detected by hypoxia probes. The proportion of CAR-T cells in the tumor, the percentage of CAR-T cells expressing hemoglobin, and the levels of reactive oxygen species and apoptosis of CAR-T cells under different conditions were detected by flow cytometry. The expression of related hemoglobin subunits in CAR-T cells was detected by WB assay. The proliferation level of cells was detected by hemocytometer, the cytotoxicity of CAR-T cells against tumor cells was detected by luciferase reporter assay, the expression level of HIF-1α in CAR-T cells was detected by qPCR, the oxygen content in T cells was detected by MitoXpress Intra kit. Results: The solid tumor models constructed from different cell lines all exhibited significant hypoxia, and the infiltration level of CAR-T cells was significantly negatively correlated with the degree of hypoxia (P < 0.000 1). HBA CAR-T and HBB CAR-T were successfully constructed (positive rate > 60%), and the corresponding hemoglobin subunits were stably expressed. Under hypoxic conditions, the ROS level and apoptosis level of HBA CAR-T and HBB CAR-T significantly decreased, and their proliferation and cytotoxicity against tumor cells were significantly stronger than those of conventional CAR-T cells (all P < 0.05). HBA CAR-T and HBB CAR-T showed decreased HIF-1α expression (all P < 0.001), and their level of hypoxia significantly decreased (all P < 0.001). Conclusion: The ectopic expression of hemoglobin can reverse the functional impairment of CAR-T cells under hypoxic conditions and enhance their cytotoxicity against tumor cells in vitro.
2026, 33(3):243-251.
DOI: 10.3872/j.issn.1007-385X.2026.03.003
Abstract:
[Abstract] Objective: To investigate the mechanism by which actin-like protein 6A (ACTL6A) regulates ferroptosis and contributes to doxorubicin (DOX) resistance in diffuse large B cell lymphoma (DLBCL) cells. Methods: The parental DLBCL cell line SU-DHL-4 cells and its DOX-resistant variant SU-DHL-4/DOX cells were cultured. Changes in the expression of ACTL6A were detected by qPCR and WB assay. SU-DHL-4/DOX cells with ACTL6A knockdown were constructed by transfecting plasmids carrying a short hairpin RNA targeting ACTL6A (sh-ACTL6A) or its negative control (sh-NC). The expression levels of ACTL6A and ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase longchain family member 4 (ACSL4), were measured using qPCR and WB. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were performed to verify the targeting and regulatory relationship between ACTL6A and GPX4. SU-DHL-4/DOX cells were divided into Control, sh-NC, sh-ACTL6A, sh-NC + oe-GPX4, and sh-ACTL6A + oe-GPX4 groups. Corresponding plasmids were transfected into the cells. CCK-8 assay was used to detect cell survival rates of each group under different concentrations of DOX treatment. FerroOrange, Liperfluo, and DCFH-DA probes were used to detect ferrous ion (Fe2+) levels, lipid peroxidation, and reactive oxygen species (ROS) in each group of cells, respectively. A colorimetric method was used to measure the contents of glutathione (GSH) and malondialdehyde (MDA) in each group of cells. Results: Both ACTL6A mRNA and protein were highly expressed in SU-DHL-4/DOX cells (both P < 0.05), compared to SU-DHL-4 cells. ACTL6A and GPX4 have a targeting binding relationship. Knockdown of ACTL6A significantly decreased the mRNA and protein expression of ACTL6A and GPX4 in SU-DHL-4/DOX cells (both P < 0.05), indicating that ACTL6A regulates GPX4 expression. Knockdown of ACTL6A significantly inhibited the survival of SU-DHL-4/DOX cells, increased intracellular Fe2+, lipid peroxides, ROS, and MDA levels, and inhibited GSH production (all P < 0.05). However, overexpression of GPX4 in ACTL6A-knockdown cells upregulated the mRNA and protein expression levels of GPX4 in SU-DHL-4/DOX cells (both P < 0.05), increased cell survival rate, inhibited the production of intracellular Fe2+, lipid peroxides, ROS, and MDA, and increased GSH production (all P < 0.05). Conclusion: ACTL6A is highly expressed in DOX-resistant DLBCL cells. By regulating GPX4 expression, ACTL6A inhibits ferroptosis and promotes drug resistance in DLBCL cells.
[Abstract] Objective: To investigate the mechanism by which actin-like protein 6A (ACTL6A) regulates ferroptosis and contributes to doxorubicin (DOX) resistance in diffuse large B cell lymphoma (DLBCL) cells. Methods: The parental DLBCL cell line SU-DHL-4 cells and its DOX-resistant variant SU-DHL-4/DOX cells were cultured. Changes in the expression of ACTL6A were detected by qPCR and WB assay. SU-DHL-4/DOX cells with ACTL6A knockdown were constructed by transfecting plasmids carrying a short hairpin RNA targeting ACTL6A (sh-ACTL6A) or its negative control (sh-NC). The expression levels of ACTL6A and ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase longchain family member 4 (ACSL4), were measured using qPCR and WB. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were performed to verify the targeting and regulatory relationship between ACTL6A and GPX4. SU-DHL-4/DOX cells were divided into Control, sh-NC, sh-ACTL6A, sh-NC + oe-GPX4, and sh-ACTL6A + oe-GPX4 groups. Corresponding plasmids were transfected into the cells. CCK-8 assay was used to detect cell survival rates of each group under different concentrations of DOX treatment. FerroOrange, Liperfluo, and DCFH-DA probes were used to detect ferrous ion (Fe2+) levels, lipid peroxidation, and reactive oxygen species (ROS) in each group of cells, respectively. A colorimetric method was used to measure the contents of glutathione (GSH) and malondialdehyde (MDA) in each group of cells. Results: Both ACTL6A mRNA and protein were highly expressed in SU-DHL-4/DOX cells (both P < 0.05), compared to SU-DHL-4 cells. ACTL6A and GPX4 have a targeting binding relationship. Knockdown of ACTL6A significantly decreased the mRNA and protein expression of ACTL6A and GPX4 in SU-DHL-4/DOX cells (both P < 0.05), indicating that ACTL6A regulates GPX4 expression. Knockdown of ACTL6A significantly inhibited the survival of SU-DHL-4/DOX cells, increased intracellular Fe2+, lipid peroxides, ROS, and MDA levels, and inhibited GSH production (all P < 0.05). However, overexpression of GPX4 in ACTL6A-knockdown cells upregulated the mRNA and protein expression levels of GPX4 in SU-DHL-4/DOX cells (both P < 0.05), increased cell survival rate, inhibited the production of intracellular Fe2+, lipid peroxides, ROS, and MDA, and increased GSH production (all P < 0.05). Conclusion: ACTL6A is highly expressed in DOX-resistant DLBCL cells. By regulating GPX4 expression, ACTL6A inhibits ferroptosis and promotes drug resistance in DLBCL cells.
2026, 33(3):252-261.
DOI: 10.3872/j.issn.1007-385X.2026.03.004
Abstract:
[Abstract] Objective: To investigate the cytotoxic effects and underlying mechanisms of Bufalin (Buf) on ovarian cancer cells (A2780 and SKOV3) and to evaluate its synergistic cytotoxicity with cisplatin (DDP). Methods: A2780 and SKOV3 cells were routinely cultured. The effect of Buf on cell proliferation and its half-maximal inhibitory concentration (IC50) were determined using CCK-8 assay and colony formation assay. Following treatments with various concentrations of Buf, morphological changes of tumor cells were observed under a microscope, lactate dehydrogenase (LDH) release was measured using colorimetric assay, and the proportion of Annexin Ⅴ?PI? cells was analyzed using flow cytometry. The mRNA and protein expression levels of pyroptosis-related molecules were detected using qPCR and WB, respectively. Small interfering RNA was used to knock down gasdermin D (GSDMD) in A2780 and SKOV3 cells to validate its functional role. The synergistic cytotoxic effects of Buf and DDP against A2780 and SKOV3 cells were analyzed using the SynergyFinder platform, and the underlying mechanisms were further explored using flow cytometry, qPCR, and WB. Additionally, the synergistic effect of Buf and DDP on DDP-resistant A2780 and SKOV3 cells was evaluated using flow cytometry. Results: Compared with the control group, Buf significantly inhibited proliferation and migration of ovarian cancer cells (both P < 0.05), induced LDH release and cell pyroptosis (both P < 0.05), and upregulated the mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), cysteine-aspartic acid protease 1 (CASP1), gasdermin D (GSDMD), interleukin(IL) -1β, and IL-18 (all P < 0.05). The combination of Buf and DDP synergistically inhibited the proliferation of A2780 and SKOV3 cells and further enhanced the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP. Conclusion: Buf induces pyroptosis in A2780 and SKOV3 cells by activating the NLRP3/CASP1/GSDMD signaling pathway and enhances the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP.
[Abstract] Objective: To investigate the cytotoxic effects and underlying mechanisms of Bufalin (Buf) on ovarian cancer cells (A2780 and SKOV3) and to evaluate its synergistic cytotoxicity with cisplatin (DDP). Methods: A2780 and SKOV3 cells were routinely cultured. The effect of Buf on cell proliferation and its half-maximal inhibitory concentration (IC50) were determined using CCK-8 assay and colony formation assay. Following treatments with various concentrations of Buf, morphological changes of tumor cells were observed under a microscope, lactate dehydrogenase (LDH) release was measured using colorimetric assay, and the proportion of Annexin Ⅴ?PI? cells was analyzed using flow cytometry. The mRNA and protein expression levels of pyroptosis-related molecules were detected using qPCR and WB, respectively. Small interfering RNA was used to knock down gasdermin D (GSDMD) in A2780 and SKOV3 cells to validate its functional role. The synergistic cytotoxic effects of Buf and DDP against A2780 and SKOV3 cells were analyzed using the SynergyFinder platform, and the underlying mechanisms were further explored using flow cytometry, qPCR, and WB. Additionally, the synergistic effect of Buf and DDP on DDP-resistant A2780 and SKOV3 cells was evaluated using flow cytometry. Results: Compared with the control group, Buf significantly inhibited proliferation and migration of ovarian cancer cells (both P < 0.05), induced LDH release and cell pyroptosis (both P < 0.05), and upregulated the mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), cysteine-aspartic acid protease 1 (CASP1), gasdermin D (GSDMD), interleukin(IL) -1β, and IL-18 (all P < 0.05). The combination of Buf and DDP synergistically inhibited the proliferation of A2780 and SKOV3 cells and further enhanced the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP. Conclusion: Buf induces pyroptosis in A2780 and SKOV3 cells by activating the NLRP3/CASP1/GSDMD signaling pathway and enhances the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP.
2026, 33(3):262-269.
DOI: 10.3872/j.issn.1007-385X.2026.03.005
Abstract:
[Abstract] Objective: To construct manganese porphyrin metal-organic framework nanoparticles (DPM) loaded with the STING agonist DMXAA, and to investigate their therapeutic effect against triple-negative breast cancer (TNBC) cells (4T1) and 4T1 cellmouse xenografts. Methods: DPM nanoparticles were prepared by physical adsorption. Their morphology and physicochemical properties were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and a nanoparticle size analyzer. 4T1 cells were cultured and divided into the following experimental groups: Control, Ultrasound Irradiation (US), DPM Treatment (DPM), and DPM Treatment combined with Ultrasound Irradiation (DPM + US). Cell viability was assessed using the CCK-8 assay. The expression of high mobility group box 1 (HMGB1) and calreticulin (CRT) was detected using immunofluorescence. Expression of STING pathway-related proteins was analyzed using WB. A 4T1 cell xenograft model was constructed and randomly divided into four groups. Following the treatments as those in the cell experiments, tumor volume was measured, and immunofluorescence was used to detect the expression of Ki-67, HMGB1, CRT, and hypoxia inducible factor-1ɑ (HIF-1α) in the transplanted tumor tissues. Additionally, TUNEL assay was used to detect cell apoptosis, flow cytometry was applied to assess immune cell activation, and H-E staining was used to evaluate the safety of the nanoparticles in major organs. Results: DPM exhibited a spindle shape with an average particle size of (268 ± 3.302) nm and a zeta potential of (33.1 ± 0.87) mV. In cell experiments, DPM combined with ultrasound irradiation significantly inhibited 4T1 cell growth (P < 0.001), elevated ROS levels (P < 0.001), induced upregulation of CRT expression (P < 0.001), and caused the translocation of HMGB1 from the nucleus to the cytoplasm. In addition, the STING signaling pathway was activated, as evidenced by significantly increased expression of p-STING, p-TBK1, and p-IRF3 proteins (all P < 0.001). In vivo, DPM combined with ultrasound irradiation significantly inhibited the growth of 4T1 cell xenograft (P < 0.001), promoted immune cell phenotypic transformation (P < 0.001), suppressed Ki-67 and HIF-1α expression in xenograft tissues, and reduced GSH production (P < 0.01). It also promoted CRT and HMGB1 protein expression and ROS production (P < 0.001). No significant effects on major organ structures were observed. Conclusion: DPM combined with ultrasound irradiation can significantly inhibit the growth of 4T1 cells and the xenografts through activation of the STING pathway, induce antitumor immune responses, and show no obvious toxicity to major organs.
[Abstract] Objective: To construct manganese porphyrin metal-organic framework nanoparticles (DPM) loaded with the STING agonist DMXAA, and to investigate their therapeutic effect against triple-negative breast cancer (TNBC) cells (4T1) and 4T1 cellmouse xenografts. Methods: DPM nanoparticles were prepared by physical adsorption. Their morphology and physicochemical properties were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and a nanoparticle size analyzer. 4T1 cells were cultured and divided into the following experimental groups: Control, Ultrasound Irradiation (US), DPM Treatment (DPM), and DPM Treatment combined with Ultrasound Irradiation (DPM + US). Cell viability was assessed using the CCK-8 assay. The expression of high mobility group box 1 (HMGB1) and calreticulin (CRT) was detected using immunofluorescence. Expression of STING pathway-related proteins was analyzed using WB. A 4T1 cell xenograft model was constructed and randomly divided into four groups. Following the treatments as those in the cell experiments, tumor volume was measured, and immunofluorescence was used to detect the expression of Ki-67, HMGB1, CRT, and hypoxia inducible factor-1ɑ (HIF-1α) in the transplanted tumor tissues. Additionally, TUNEL assay was used to detect cell apoptosis, flow cytometry was applied to assess immune cell activation, and H-E staining was used to evaluate the safety of the nanoparticles in major organs. Results: DPM exhibited a spindle shape with an average particle size of (268 ± 3.302) nm and a zeta potential of (33.1 ± 0.87) mV. In cell experiments, DPM combined with ultrasound irradiation significantly inhibited 4T1 cell growth (P < 0.001), elevated ROS levels (P < 0.001), induced upregulation of CRT expression (P < 0.001), and caused the translocation of HMGB1 from the nucleus to the cytoplasm. In addition, the STING signaling pathway was activated, as evidenced by significantly increased expression of p-STING, p-TBK1, and p-IRF3 proteins (all P < 0.001). In vivo, DPM combined with ultrasound irradiation significantly inhibited the growth of 4T1 cell xenograft (P < 0.001), promoted immune cell phenotypic transformation (P < 0.001), suppressed Ki-67 and HIF-1α expression in xenograft tissues, and reduced GSH production (P < 0.01). It also promoted CRT and HMGB1 protein expression and ROS production (P < 0.001). No significant effects on major organ structures were observed. Conclusion: DPM combined with ultrasound irradiation can significantly inhibit the growth of 4T1 cells and the xenografts through activation of the STING pathway, induce antitumor immune responses, and show no obvious toxicity to major organs.
2026, 33(3):270-279.
DOI: 10.3872/j.issn.1007-385X.2026.03.006
Abstract:
[Abstract] Objective: To investigate the molecular mechanisms by which Paris polyphyllaa saponin (PPⅡ) suppresses the malignant biological behaviors of thyroid cancer (TC). Methods: Thyroid cancer TPC1 cells were routinely cultured and divided into five experimental groups, designated as sh-NC, sh-lectin-galactoside binding-soluble 3 (sh-LGALS3), OE-NC, OE-LGALS3, and OELGALS3 + PPⅡ. TPC1 cells in each group were transfected with corresponding plasmids using transfection reagents.qPCR was used to detect the expression of LGALS3 mRNA in TPC1 cells. WB was performed to examine the expression of LGALS3 and PI3K/AKT signaling pathway-related proteins. CCK-8 assay, Transwell assay, wound healing assay, and flow cytometry were used to assess the proliferation, migration, invasion, and apoptosis of TPC1 cells in each group. Results: PPⅡ significantly inhibited the proliferation, migration, and invasion of TPC1 cells, while inducing apoptosis (all P < 0.000 1). Database analyses revealed that LGALS3 was highly expressed in thyroid cancer tissues (P < 0.001) and was identified as a potential target gene of PPⅡ. LGALS3 was highly expressed in TPC1 cells (P < 0.000 1). Knockdown of LGALS3 suppressed the malignant biological behaviors of TPC1 cells and promoted apoptosis (all P < 0.000 1). PPⅡ inhibited the malignant biological behaviors of TPC1 cells by downregulating LGALS3 mRNA and protein expression (P < 0.01 or P < 0.001). Furthermore, PP Ⅱ suppressed the activation of the PI3K/AKT signaling pathway by inhibiting LGALS3 expression (P < 0.001 or P < 0.000 1). LGALS3 promoted the malignant biological behaviors of TPC1 cells through the PI3K/AKT signaling pathway (P < 0.000 1). Conclusion: PPⅡ exerts anti-tumor effects in thyroid cancer by inhibiting LGALS3 expression in TPC1 cells and attenuating the overactivation of the PI3K/AKT signaling pathway.
[Abstract] Objective: To investigate the molecular mechanisms by which Paris polyphyllaa saponin (PPⅡ) suppresses the malignant biological behaviors of thyroid cancer (TC). Methods: Thyroid cancer TPC1 cells were routinely cultured and divided into five experimental groups, designated as sh-NC, sh-lectin-galactoside binding-soluble 3 (sh-LGALS3), OE-NC, OE-LGALS3, and OELGALS3 + PPⅡ. TPC1 cells in each group were transfected with corresponding plasmids using transfection reagents.qPCR was used to detect the expression of LGALS3 mRNA in TPC1 cells. WB was performed to examine the expression of LGALS3 and PI3K/AKT signaling pathway-related proteins. CCK-8 assay, Transwell assay, wound healing assay, and flow cytometry were used to assess the proliferation, migration, invasion, and apoptosis of TPC1 cells in each group. Results: PPⅡ significantly inhibited the proliferation, migration, and invasion of TPC1 cells, while inducing apoptosis (all P < 0.000 1). Database analyses revealed that LGALS3 was highly expressed in thyroid cancer tissues (P < 0.001) and was identified as a potential target gene of PPⅡ. LGALS3 was highly expressed in TPC1 cells (P < 0.000 1). Knockdown of LGALS3 suppressed the malignant biological behaviors of TPC1 cells and promoted apoptosis (all P < 0.000 1). PPⅡ inhibited the malignant biological behaviors of TPC1 cells by downregulating LGALS3 mRNA and protein expression (P < 0.01 or P < 0.001). Furthermore, PP Ⅱ suppressed the activation of the PI3K/AKT signaling pathway by inhibiting LGALS3 expression (P < 0.001 or P < 0.000 1). LGALS3 promoted the malignant biological behaviors of TPC1 cells through the PI3K/AKT signaling pathway (P < 0.000 1). Conclusion: PPⅡ exerts anti-tumor effects in thyroid cancer by inhibiting LGALS3 expression in TPC1 cells and attenuating the overactivation of the PI3K/AKT signaling pathway.
2026, 33(3):280-287.
DOI: 10.3872/j.issn.1007-385X.2026.03.007
Abstract:
[Abstract] Objective: To investigate the mechanism by which IL-2 promotes bladder cancer cell resistance by impairing NK cell function via the STAT3 signalling axis. Methods: Bladder cancer T24 cells were routinely cultured, and cisplatin-resistant T24/DDP cells were established through stepwise dose-escalation method. Cells were divided into the following groups: control, DDP, IL-22, IL-22 + DDP, IL-22 + anti-IL-22, and IL-22 + DDP + Stattic (a STAT3 inhibitor). The mRNA expression of IL-22, cyclin D1, and BCL2 was detected using qRT-PCR. Protein expression of BAX, BCL2, and phosphorylated STAT3 (p-STAT3) was analyzed using WB. Cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. The levels of lactate dehydrogenase (LDH), TNF-α, IFN-γ, granzyme B (GzmB), and perforin (PRF) in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA). Results: T24/DDP cells exhibited significantly reduced sensitivity to DDP (P < 0.05), accompanied by markedly elevated expression levels of drug resistance-associated genes (P-glycoprotein[P-gp]，lung drug resistance protein[LRP],and multidrug resistance-associated protein 1[MRP1]), as well as IL-22 and its receptor (all P < 0.05), indicating successful establishment of DDP-resistant cells. Compared with the control group, the DDP group showed decreased proliferation, increased apoptosis, upregulated BAX protein expression, and downregulated Bcl-2 protein expression in T24 cells (all P < 0.05). Compared with the DDP group, the IL-22 + DDP group showed significantly increased proliferative activity, decreased apoptosis rate, downregulated BAX, and upregulated BCL expression (all P < 0.05), suggesting that IL-22 promotes DDP resistance in T24 cells by modulating BAX/BCL2 expression. Compared with the control group, IL-22 stimulation significantly increased total and nuclear p-STAT3 expression in T24 cells (all P < 0.05), and this increase was significantly attenuated by pre-treatment with an IL-22 neutralizing antibody (IL-22 + anti-IL-22 group) (P < 0.05), indicating that IL-22 activates STAT3 phosphorylation and promotes its nuclear translocation in T24 cells. In the T24-NK92 co-culture system, the levels of LDH, TNF-α, IFN-γ, GzmB, and PRF in the supernatant were significantly increased in the DDP group compared with the control group (all P < 0.05). Co-treatment with IL-22 and DDP significantly reduced the levels of these cytotoxicity-related factors compared to the DDP group (all P < 0.05). Furthermore, IL-22 treatment alone significantly decreased the levels of these factors compared to the control group (all P < 0.05), while the addition of the STAT3 inhibitor Stattic (IL-22 + Stattic group) reversed this suppression, leading to significant elevations in these factors (all P < 0.05). These findings indicate that IL-22 diminishes the cytotoxicity of NK92 cells against T24 cells, which can be reversed by STAT3 inhibition. Regarding chemoresistance, T24 cell proliferative activity was significantly higher in the IL-22 + DDP group than in the DDP group (P < 0.05). This enhancement was abolished by Stattic, as evidenced by significantly lower activity in the IL-22 + DDP + Stattic group compared to the IL-22 + DDP group (P < 0.05). Consistently, the apoptosis rate was significantly decreased in the IL-22 + DDP group compared with the DDP group (P < 0.05), and Stattic co-treatment significantly increased the apoptosis rate compared to the IL-22 + DDP group (P < 0.05). These findings indicate that IL-22 regulates both DDP resistance in T24 cells and NK cell-mediated immune function via the STAT3 pathway. Conclusion: IL-22 promotes DDP resistance in T24 bladder cancer cells and suppresses NK cell function via activating the STAT3 signaling axis.
[Abstract] Objective: To investigate the mechanism by which IL-2 promotes bladder cancer cell resistance by impairing NK cell function via the STAT3 signalling axis. Methods: Bladder cancer T24 cells were routinely cultured, and cisplatin-resistant T24/DDP cells were established through stepwise dose-escalation method. Cells were divided into the following groups: control, DDP, IL-22, IL-22 + DDP, IL-22 + anti-IL-22, and IL-22 + DDP + Stattic (a STAT3 inhibitor). The mRNA expression of IL-22, cyclin D1, and BCL2 was detected using qRT-PCR. Protein expression of BAX, BCL2, and phosphorylated STAT3 (p-STAT3) was analyzed using WB. Cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. The levels of lactate dehydrogenase (LDH), TNF-α, IFN-γ, granzyme B (GzmB), and perforin (PRF) in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA). Results: T24/DDP cells exhibited significantly reduced sensitivity to DDP (P < 0.05), accompanied by markedly elevated expression levels of drug resistance-associated genes (P-glycoprotein[P-gp]，lung drug resistance protein[LRP],and multidrug resistance-associated protein 1[MRP1]), as well as IL-22 and its receptor (all P < 0.05), indicating successful establishment of DDP-resistant cells. Compared with the control group, the DDP group showed decreased proliferation, increased apoptosis, upregulated BAX protein expression, and downregulated Bcl-2 protein expression in T24 cells (all P < 0.05). Compared with the DDP group, the IL-22 + DDP group showed significantly increased proliferative activity, decreased apoptosis rate, downregulated BAX, and upregulated BCL expression (all P < 0.05), suggesting that IL-22 promotes DDP resistance in T24 cells by modulating BAX/BCL2 expression. Compared with the control group, IL-22 stimulation significantly increased total and nuclear p-STAT3 expression in T24 cells (all P < 0.05), and this increase was significantly attenuated by pre-treatment with an IL-22 neutralizing antibody (IL-22 + anti-IL-22 group) (P < 0.05), indicating that IL-22 activates STAT3 phosphorylation and promotes its nuclear translocation in T24 cells. In the T24-NK92 co-culture system, the levels of LDH, TNF-α, IFN-γ, GzmB, and PRF in the supernatant were significantly increased in the DDP group compared with the control group (all P < 0.05). Co-treatment with IL-22 and DDP significantly reduced the levels of these cytotoxicity-related factors compared to the DDP group (all P < 0.05). Furthermore, IL-22 treatment alone significantly decreased the levels of these factors compared to the control group (all P < 0.05), while the addition of the STAT3 inhibitor Stattic (IL-22 + Stattic group) reversed this suppression, leading to significant elevations in these factors (all P < 0.05). These findings indicate that IL-22 diminishes the cytotoxicity of NK92 cells against T24 cells, which can be reversed by STAT3 inhibition. Regarding chemoresistance, T24 cell proliferative activity was significantly higher in the IL-22 + DDP group than in the DDP group (P < 0.05). This enhancement was abolished by Stattic, as evidenced by significantly lower activity in the IL-22 + DDP + Stattic group compared to the IL-22 + DDP group (P < 0.05). Consistently, the apoptosis rate was significantly decreased in the IL-22 + DDP group compared with the DDP group (P < 0.05), and Stattic co-treatment significantly increased the apoptosis rate compared to the IL-22 + DDP group (P < 0.05). These findings indicate that IL-22 regulates both DDP resistance in T24 cells and NK cell-mediated immune function via the STAT3 pathway. Conclusion: IL-22 promotes DDP resistance in T24 bladder cancer cells and suppresses NK cell function via activating the STAT3 signaling axis.
2026, 33(3):288-295.
DOI: 10.3872/j.issn.1007-385X.2026.03.008
Abstract:
[Abstract] Objective: To investigate the enhanced cytotoxic effect of circular nucleic acid aptamer-drug conjugates (ApDC) combined with anti-CD19 chimeric antigen receptor T/NK (CAR19-T/NK) cells on Nalm6 leukemia cells. Methods: Database analysis was used to identify the marker protein tyrosine kinase 7 (PTK7) in leukemia cells. An aptamer targeting PTK7, sgc8, was designed and synthesized. Subsequently, two ApDCs were prepared: nucleic acid aptamer-conjugated gemcitabine (sgc8-GEM) and circular nucleic acid aptamer-conjugated gemcitabine (C-sgc8-GEM). Their stability was analyzed using agarose gel electrophoresis. Human peripheral blood T/NK cells were transfected with CD19-CAR overexpression lentivirus to construct CAR19-T and CAR19-NK cells. The binding affinity of sgc8 to Nalm6 cells was detected using flow cytometry. The cytotoxicity of sgc8-GEM, C-sgc8-GEM, and their combination with CAR19-T or CAR19-NK cells against Nalm6 cells was evaluated using CCK-8 assay and flow cytometry. Results: PTK7 mRNA was highly expressed in leukemia cells (P < 0.01). C-sgc8-GEM exhibited higher stability than sgc8-GEM, and sgc8-GEM exhibited more effective cytotoxicity against Nalm6 cells compared to GEM alone (P < 0.001). The combination of C-sgc8-GEM or sgc8-GEM with CAR19-T/NK cells showed significantly stronger cytotoxicity against Nalm6 cells than C-sgc8-GEM, sgc8-GEM, or CAR19-T/ NK cells alone (P < 0.001). Conclusion: The circular ApDCs combined with CAR19-T/NK cells were successfully developed. This dual-targeting strategy effectively increased the cytotoxicity against Nalm6 cells, providing a new treatment approach for acute lymphoblastic leukemia.
[Abstract] Objective: To investigate the enhanced cytotoxic effect of circular nucleic acid aptamer-drug conjugates (ApDC) combined with anti-CD19 chimeric antigen receptor T/NK (CAR19-T/NK) cells on Nalm6 leukemia cells. Methods: Database analysis was used to identify the marker protein tyrosine kinase 7 (PTK7) in leukemia cells. An aptamer targeting PTK7, sgc8, was designed and synthesized. Subsequently, two ApDCs were prepared: nucleic acid aptamer-conjugated gemcitabine (sgc8-GEM) and circular nucleic acid aptamer-conjugated gemcitabine (C-sgc8-GEM). Their stability was analyzed using agarose gel electrophoresis. Human peripheral blood T/NK cells were transfected with CD19-CAR overexpression lentivirus to construct CAR19-T and CAR19-NK cells. The binding affinity of sgc8 to Nalm6 cells was detected using flow cytometry. The cytotoxicity of sgc8-GEM, C-sgc8-GEM, and their combination with CAR19-T or CAR19-NK cells against Nalm6 cells was evaluated using CCK-8 assay and flow cytometry. Results: PTK7 mRNA was highly expressed in leukemia cells (P < 0.01). C-sgc8-GEM exhibited higher stability than sgc8-GEM, and sgc8-GEM exhibited more effective cytotoxicity against Nalm6 cells compared to GEM alone (P < 0.001). The combination of C-sgc8-GEM or sgc8-GEM with CAR19-T/NK cells showed significantly stronger cytotoxicity against Nalm6 cells than C-sgc8-GEM, sgc8-GEM, or CAR19-T/ NK cells alone (P < 0.001). Conclusion: The circular ApDCs combined with CAR19-T/NK cells were successfully developed. This dual-targeting strategy effectively increased the cytotoxicity against Nalm6 cells, providing a new treatment approach for acute lymphoblastic leukemia.
2026, 33(3):296-312.
DOI: 10.3872/j.issn.1007-385X.2026.03.009
Abstract:
[Abstract] Objective: To investigate the predictive value of eosinophils (Eos), other circulating blood cells, and inflammatory markers for the efficacy of immunotherapy and immune-related adverse events (irAEs) in small cell lung cancer (SCLC). Methods: A retrospective analysis was conducted on the clinical information of 410 SCLC patients admitted to the Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Second Military Medical University between August 2013 and July 2023. Complete blood cell counts and cytokine levels were measured before chemotherapy/immunotherapy and after three treatment cycles. The onset time, type, grade, and follow-up information of irAEs were recorded. Results: Among the patients, 116 received chemotherapy combined with immune checkpoint inhibitors (ICIs), including 91 with first-line treatment and 25 with later-line treatment. The overall response rate (ORR) was 44.8% and the disease control rate (DCR) was 90.5% in the combination group, compared to 38.4% and 85.0%, respectively, in the chemotherapy-alone group. The median progression-free survival (PFS) was 8.9 (7.2-10.5) months and median overall survival (OS) was 17.7 (13.9-21.5) months in the combination group. After propensity score matching (PSM) between the combination and chemotherapy-alone groups, the levels of absolute eosinophil count (AEC) and relative eosinophil count (REC) after three treatment cycles were compared. Ratios of follow-up Eos levels to baseline levels (AECT1/0, AECT2/0, AECT3/0, RECT1/0, RECT2/0, RECT3/0) were calculated, and the results showed that AECT3/0 and RECT3/0 in the combination group were significantly higher than those in the chemotherapy-alone group. Univariate analysis showed that elevated baseline AEC and REC were significantly associated with better time to treatment failure (TTF) and OS (P < 0.05). The ratio of post-treatment to baseline Eos levels (AECT3/0, RECT3/0) was significantly associated with better PFS and TTF (P < 0.05). Elevated RECT3/0 was also significantly associated with improved OS (P < 0.05). Multivariate analysis indicated that AECT3/0 > 0.41 was significantly associated with better PFS and TTF (P < 0.05), RECT3/0 > 0.32 was significantly associated with better PFS, TTF, and OS (P < 0.05), while RECT3/0 > 0.27 was only significantly associated with better TTF and OS (P < 0.05). Subgroup analysis revealed that RECT3/0 was significantly higher in the response group than in the non-response group (P < 0.05). There was no statistical difference in PFS, TTF, or OS between patients receiving first-line versus second-/later-line ICI therapy. However, ORR (50% vs 25%, P < 0.05) and DCR (93.48% vs 79.17%, P < 0.05) were significantly superior with first-line ICI use. Among the 116 patients in the combination group, 43 (35.34%) experienced irAEs, most commonly immune-related dermatitis (8.62%). Grade Ⅲ or higher irAEs occurred in 17 patients (14.66%), leading to treatment discontinuation in 10 cases (8.62%) and deaths in 2 cases. Patients who experienced irAEs had significantly longer PFS compared to those without irAEs (P < 0.05), while TTF and OS were not significantly different. RECT3 levels were significantly higher in patients with irAEs than in those without (P < 0.05), and AECT3/0 > 0.29 was associated with a significantly higher incidence of irAEs (P < 0.05). Conclusion: Eosinophils represent a protective factor in SCLC patients receiving ICI therapy. Monitoring AECT3/0 and RECT3/0, combined with patient clinicopathological characteristics, cytokines, and inflammatory markers, can effectively predict immunotherapy efficacy and the occurrence of irAEs in SCLC patients.
[Abstract] Objective: To investigate the predictive value of eosinophils (Eos), other circulating blood cells, and inflammatory markers for the efficacy of immunotherapy and immune-related adverse events (irAEs) in small cell lung cancer (SCLC). Methods: A retrospective analysis was conducted on the clinical information of 410 SCLC patients admitted to the Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Second Military Medical University between August 2013 and July 2023. Complete blood cell counts and cytokine levels were measured before chemotherapy/immunotherapy and after three treatment cycles. The onset time, type, grade, and follow-up information of irAEs were recorded. Results: Among the patients, 116 received chemotherapy combined with immune checkpoint inhibitors (ICIs), including 91 with first-line treatment and 25 with later-line treatment. The overall response rate (ORR) was 44.8% and the disease control rate (DCR) was 90.5% in the combination group, compared to 38.4% and 85.0%, respectively, in the chemotherapy-alone group. The median progression-free survival (PFS) was 8.9 (7.2-10.5) months and median overall survival (OS) was 17.7 (13.9-21.5) months in the combination group. After propensity score matching (PSM) between the combination and chemotherapy-alone groups, the levels of absolute eosinophil count (AEC) and relative eosinophil count (REC) after three treatment cycles were compared. Ratios of follow-up Eos levels to baseline levels (AECT1/0, AECT2/0, AECT3/0, RECT1/0, RECT2/0, RECT3/0) were calculated, and the results showed that AECT3/0 and RECT3/0 in the combination group were significantly higher than those in the chemotherapy-alone group. Univariate analysis showed that elevated baseline AEC and REC were significantly associated with better time to treatment failure (TTF) and OS (P < 0.05). The ratio of post-treatment to baseline Eos levels (AECT3/0, RECT3/0) was significantly associated with better PFS and TTF (P < 0.05). Elevated RECT3/0 was also significantly associated with improved OS (P < 0.05). Multivariate analysis indicated that AECT3/0 > 0.41 was significantly associated with better PFS and TTF (P < 0.05), RECT3/0 > 0.32 was significantly associated with better PFS, TTF, and OS (P < 0.05), while RECT3/0 > 0.27 was only significantly associated with better TTF and OS (P < 0.05). Subgroup analysis revealed that RECT3/0 was significantly higher in the response group than in the non-response group (P < 0.05). There was no statistical difference in PFS, TTF, or OS between patients receiving first-line versus second-/later-line ICI therapy. However, ORR (50% vs 25%, P < 0.05) and DCR (93.48% vs 79.17%, P < 0.05) were significantly superior with first-line ICI use. Among the 116 patients in the combination group, 43 (35.34%) experienced irAEs, most commonly immune-related dermatitis (8.62%). Grade Ⅲ or higher irAEs occurred in 17 patients (14.66%), leading to treatment discontinuation in 10 cases (8.62%) and deaths in 2 cases. Patients who experienced irAEs had significantly longer PFS compared to those without irAEs (P < 0.05), while TTF and OS were not significantly different. RECT3 levels were significantly higher in patients with irAEs than in those without (P < 0.05), and AECT3/0 > 0.29 was associated with a significantly higher incidence of irAEs (P < 0.05). Conclusion: Eosinophils represent a protective factor in SCLC patients receiving ICI therapy. Monitoring AECT3/0 and RECT3/0, combined with patient clinicopathological characteristics, cytokines, and inflammatory markers, can effectively predict immunotherapy efficacy and the occurrence of irAEs in SCLC patients.
2026, 33(3):313-322.
DOI: 10.3872/j.issn.1007-385X.2026.03.010
Abstract:
[Abstract] Objective: To investigate the dynamic changes and predictive value of peripheral blood T helper 1 (Th1)/Th2/Th17-related cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17A for treatment efficacy and prognosis in patients with stage Ⅲ-Ⅳ lung squamous cell carcinoma (LSCC) undergoing first-line immunotherapy combined with chemotherapy. Methods: Clinical data of 58 patients with stage Ⅲ-Ⅳ LSCC who received first-line immunotherapy combined with chemotherapy at the Affiliated Hospital of Inner Mongolia Medical University from January 2020 to December 2023 were retrospectively analyzed. Peripheral blood samples were collected at baseline, after 2, 4, and 6 treatment cycles, and at disease progression. Th1/Th2/Th17 cytokine levels were measured using flow cytometry. Receiver operating characteristic (ROC) curves were used to determine optimal baseline cut-off values, based on which patients were divided into high- and low-expression groups. According to RECIST 1.1 criteria, patients were categorized into objective response rate (ORR; complete remission [CR] + partial remission [PR]) and non-ORR (stable disease [SD]+ progressive disease [PD]) groups, as well as disease control rate (DCR; CR+PR+SD) and non-DCR (PD) groups. Based on PD-L1 expression scores, patients were divided into PD-L1 ≥ 1% and PD-L1<1% or unknown groups. Differences in treatment efficacy between groups were compared, and correlations between clinicopathological characteristics and efficacy were analyzed. Generalized estimating equations (GEE) were used to assess the relationship between cytokine dynamics and treatment efficacy. Survival curves were plotted using the Kaplan-Meier method, with Log-rank tests for intergroup comparisons. Univariate and multivariate prognostic analyses were performed using COX proportional hazards regression. Results: Patients with high baseline IL-2 or IFN-γ expression demonstrated significantly higher ORRs than those with low expression (P < 0.001). The DCRs were significantly higher in the IL-2-high, IFN-γ-high, IL-10-low, and TNF-α-low groups compared with their counterparts (P < 0.001). The DCRs were significantly higher in patients with PD-L1 ≥ 1% than those with PD-L1 < 1% or unknown group (P < 0.001). Dynamic analysis revealed that serum IL-6 levels at cycles 4 and 6 were significantly lower in the response group and disease-controlled group compared with the non-response group and uncontrolled group (P < 0.05 or P < 0.001). IFN- γ levels were significantly higher in the response group than in the non-response group at baseline and cycle 6 (P < 0.05), and higher in disease-controlled group than in the uncontrolled group at baseline (P < 0.05). Survival analysis showed significantly shorter median progression-free survival (PFS) in patients with low IL-2, high IL-10, high TNF- α, and low IFN- γ expression (all P < 0.05). Multivariate COX analysis identified baseline IL-2 < 2.45 pg/mL and IL-10 ≥ 3.52 pg/mL as independent risk factors for PFS. Conclusion: Baseline levels and dynamic changes of peripheral blood Th1/Th2/Th17 cell-related cytokines have predictive value for treatment efficacy and prognosis in patients with stage Ⅲ–Ⅳ LSCC receiving first-line immunotherapy combined with chemotherapy.
[Abstract] Objective: To investigate the dynamic changes and predictive value of peripheral blood T helper 1 (Th1)/Th2/Th17-related cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17A for treatment efficacy and prognosis in patients with stage Ⅲ-Ⅳ lung squamous cell carcinoma (LSCC) undergoing first-line immunotherapy combined with chemotherapy. Methods: Clinical data of 58 patients with stage Ⅲ-Ⅳ LSCC who received first-line immunotherapy combined with chemotherapy at the Affiliated Hospital of Inner Mongolia Medical University from January 2020 to December 2023 were retrospectively analyzed. Peripheral blood samples were collected at baseline, after 2, 4, and 6 treatment cycles, and at disease progression. Th1/Th2/Th17 cytokine levels were measured using flow cytometry. Receiver operating characteristic (ROC) curves were used to determine optimal baseline cut-off values, based on which patients were divided into high- and low-expression groups. According to RECIST 1.1 criteria, patients were categorized into objective response rate (ORR; complete remission [CR] + partial remission [PR]) and non-ORR (stable disease [SD]+ progressive disease [PD]) groups, as well as disease control rate (DCR; CR+PR+SD) and non-DCR (PD) groups. Based on PD-L1 expression scores, patients were divided into PD-L1 ≥ 1% and PD-L1<1% or unknown groups. Differences in treatment efficacy between groups were compared, and correlations between clinicopathological characteristics and efficacy were analyzed. Generalized estimating equations (GEE) were used to assess the relationship between cytokine dynamics and treatment efficacy. Survival curves were plotted using the Kaplan-Meier method, with Log-rank tests for intergroup comparisons. Univariate and multivariate prognostic analyses were performed using COX proportional hazards regression. Results: Patients with high baseline IL-2 or IFN-γ expression demonstrated significantly higher ORRs than those with low expression (P < 0.001). The DCRs were significantly higher in the IL-2-high, IFN-γ-high, IL-10-low, and TNF-α-low groups compared with their counterparts (P < 0.001). The DCRs were significantly higher in patients with PD-L1 ≥ 1% than those with PD-L1 < 1% or unknown group (P < 0.001). Dynamic analysis revealed that serum IL-6 levels at cycles 4 and 6 were significantly lower in the response group and disease-controlled group compared with the non-response group and uncontrolled group (P < 0.05 or P < 0.001). IFN- γ levels were significantly higher in the response group than in the non-response group at baseline and cycle 6 (P < 0.05), and higher in disease-controlled group than in the uncontrolled group at baseline (P < 0.05). Survival analysis showed significantly shorter median progression-free survival (PFS) in patients with low IL-2, high IL-10, high TNF- α, and low IFN- γ expression (all P < 0.05). Multivariate COX analysis identified baseline IL-2 < 2.45 pg/mL and IL-10 ≥ 3.52 pg/mL as independent risk factors for PFS. Conclusion: Baseline levels and dynamic changes of peripheral blood Th1/Th2/Th17 cell-related cytokines have predictive value for treatment efficacy and prognosis in patients with stage Ⅲ–Ⅳ LSCC receiving first-line immunotherapy combined with chemotherapy.
2026, 33(3):323-328.
DOI: 10.3872/j.issn.1007-385X.2026.03.011
Abstract:
[摘 要] 免疫治疗在多个瘤种中取得显著进展，但仍面临疗效有限、耐药频发等挑战。近年来，生物物理信号对免疫治疗核心 效应细胞CD8? T细胞抗肿瘤免疫功能的调控作用备受关注。本文系统综述生物物理信号（尤其是细胞外基质与肿瘤细胞硬度） 对CD8? T细胞的调控机制，总结靶向该信号提升免疫治疗疗效的策略，展望基础研究与临床转化中的关键问题与方向。未来， 靶向生物物理信号有望成为增强免疫治疗效果的新兴突破口，为精准抗肿瘤免疫干预提供全新思路。
[摘 要] 免疫治疗在多个瘤种中取得显著进展，但仍面临疗效有限、耐药频发等挑战。近年来，生物物理信号对免疫治疗核心 效应细胞CD8? T细胞抗肿瘤免疫功能的调控作用备受关注。本文系统综述生物物理信号（尤其是细胞外基质与肿瘤细胞硬度） 对CD8? T细胞的调控机制，总结靶向该信号提升免疫治疗疗效的策略，展望基础研究与临床转化中的关键问题与方向。未来， 靶向生物物理信号有望成为增强免疫治疗效果的新兴突破口，为精准抗肿瘤免疫干预提供全新思路。
2026, 33(3):329-334.
DOI: 10.3872/j.issn.1007-385X.2026.03.012
Abstract:
[摘 要] NK细胞功能耗竭是导致肿瘤免疫逃逸的重要因素，其中肿瘤微环境（TME）中的转化生长因子（TGF）-β是诱导NK细 胞耗竭的关键因子。为逆转TGF-β的抑制作用，目前研究主要聚焦于两大方向：在细胞工程方面，通过受体阻断及下游信号重定 向等手段增强NK细胞对抑制信号的抵抗能力；在药物干预方面，用直接中和TGF-β、重编程TME，以及阻断其上游活化通路等策 略，以恢复NK细胞的抗肿瘤功能。本文综述基于NK细胞的工程化策略及靶向TGF-β通路的相关药物研究进展，对未来治疗方 向的优化进行展望，以期为推进NK细胞的肿瘤免疫治疗提供参考。
[摘 要] NK细胞功能耗竭是导致肿瘤免疫逃逸的重要因素，其中肿瘤微环境（TME）中的转化生长因子（TGF）-β是诱导NK细 胞耗竭的关键因子。为逆转TGF-β的抑制作用，目前研究主要聚焦于两大方向：在细胞工程方面，通过受体阻断及下游信号重定 向等手段增强NK细胞对抑制信号的抵抗能力；在药物干预方面，用直接中和TGF-β、重编程TME，以及阻断其上游活化通路等策 略，以恢复NK细胞的抗肿瘤功能。本文综述基于NK细胞的工程化策略及靶向TGF-β通路的相关药物研究进展，对未来治疗方 向的优化进行展望，以期为推进NK细胞的肿瘤免疫治疗提供参考。
2026, 33(3):335-341.
DOI: 10.3872/j.issn.1007-385X.2026.03.013
Abstract:
[摘 要] 免疫疗法利用患者的免疫系统来对抗疾病，是一种极具前景的治疗手段。抗体募集分子（ARM）作为一种新型免疫策 略，由识别肿瘤细胞的肿瘤结合末端（TBT）和识别内源性抗体的抗体结合末端（ABT）组成，可招募血液中的内源性抗体至肿瘤， 进而招募效应细胞，特异性引发针对恶性肿瘤的固有免疫反应。近期研究表明，在经典ARM的基础上，通过多样化的修饰和优 化，ARM的研发取得了实质性进展。本文综述了ARM的基本结构和作用机制，重点介绍其在肿瘤治疗领域内的最新进展，并探 讨未来基于ARM的免疫治疗策略可能取得突破的方向。
[摘 要] 免疫疗法利用患者的免疫系统来对抗疾病，是一种极具前景的治疗手段。抗体募集分子（ARM）作为一种新型免疫策 略，由识别肿瘤细胞的肿瘤结合末端（TBT）和识别内源性抗体的抗体结合末端（ABT）组成，可招募血液中的内源性抗体至肿瘤， 进而招募效应细胞，特异性引发针对恶性肿瘤的固有免疫反应。近期研究表明，在经典ARM的基础上，通过多样化的修饰和优 化，ARM的研发取得了实质性进展。本文综述了ARM的基本结构和作用机制，重点介绍其在肿瘤治疗领域内的最新进展，并探 讨未来基于ARM的免疫治疗策略可能取得突破的方向。
2026, 33(3):342-349.
DOI: 10.3872/j.issn.1007-385X.2026.03.014
Abstract:
[摘 要] 随着肿瘤免疫治疗技术的发展，临床上基于免疫检查点抑制剂（ICI）的免疫疗法治疗肺癌疗效较好，延长了肺癌患者 的无进展生存期。随着治疗患者的增多，发现只有少部分患者表现出持久的应答反应，因此，筛选更多免疫检查点分子来提高免 疫应答率，突破耐药的局限性至关重要。美国FDA批准使用的瑞拉利单抗可高亲和力结合淋巴细胞活化基因-3（LAG-3），抑制 其与MHCⅡ的结合，从而阻断免疫抑制性信号的传递，在肺癌的联合疗法中发挥突出作用；同时，LAG-3高表达也与肺癌不良预 后相关，有望成为ICI阻断疗法疗效监测的生物标志物。为促进靶向LAG-3的研究与临床应用，本文综述LAG-3的作用机制、 LAG-3抑制剂治疗晚期肺癌的临床试验进展，深入探讨相关毒性管理方案，并对未来可能的临床转化方向提出展望。
[摘 要] 随着肿瘤免疫治疗技术的发展，临床上基于免疫检查点抑制剂（ICI）的免疫疗法治疗肺癌疗效较好，延长了肺癌患者 的无进展生存期。随着治疗患者的增多，发现只有少部分患者表现出持久的应答反应，因此，筛选更多免疫检查点分子来提高免 疫应答率，突破耐药的局限性至关重要。美国FDA批准使用的瑞拉利单抗可高亲和力结合淋巴细胞活化基因-3（LAG-3），抑制 其与MHCⅡ的结合，从而阻断免疫抑制性信号的传递，在肺癌的联合疗法中发挥突出作用；同时，LAG-3高表达也与肺癌不良预 后相关，有望成为ICI阻断疗法疗效监测的生物标志物。为促进靶向LAG-3的研究与临床应用，本文综述LAG-3的作用机制、 LAG-3抑制剂治疗晚期肺癌的临床试验进展，深入探讨相关毒性管理方案，并对未来可能的临床转化方向提出展望。
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.