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Volume 33,Issue 5,2026 Table of Contents
2026, 33(5):477-485.
DOI: 10.3872/j.issn.1007-385X.2026.05.001
Abstract:
[Abstract] Dendritic cells (DCs) serve as the central hub connecting innate immunity and adaptive immunity, and their functional homeostasis is critical for mediating tumor immune surveillance. However, the tumor microenvironment (TME) drives metabolic reprogramming in DCs through competition for nutrients and accumulation of immunosuppressive metabolites, thereby inducing · · 477 中国肿瘤生物治疗杂志, 2026, 33(5) defects in antitumor immune responses. This article systematically reviews the remodeling mechanisms of DC subsets across three major metabolic dimensions in the TME: in glucose metabolism, lactate-rich microenvironments suppress MHC class Ⅱ molecule expression via GPR81 signaling, impairing the antigen-presenting capacity of conventional DCs (cDCs); in lipid metabolism, fatty acid oxidation mediated by the Wnt5a-β-catenin-PPARγ-CPT1A axis promotes the polarization of cDCs toward an immunosuppressive phenotype; and in amino acid metabolism, cascade activation of the Arg1-IDO1 pathway induces DCs to acquire a tolerogenic phenotype. In response to these metabolic abnormalities, current intervention strategies have expanded from single-target modulation to multimodal combination approaches, including lipid nanoparticle-based in situ vaccines and mRNA delivery systems, metabolic- immune synergistic blockade, and metabolically optimized DC vaccines. Therefore, deepening the understanding and targeting of DC metabolic checkpoints not only holds promise for reversing the immunosuppressive microenvironment and overcoming therapeutic resistance, but also provides important scientific rationale and translational strategies for developing next-generation metabolic-immune combination therapies.
[Abstract] Dendritic cells (DCs) serve as the central hub connecting innate immunity and adaptive immunity, and their functional homeostasis is critical for mediating tumor immune surveillance. However, the tumor microenvironment (TME) drives metabolic reprogramming in DCs through competition for nutrients and accumulation of immunosuppressive metabolites, thereby inducing · · 477 中国肿瘤生物治疗杂志, 2026, 33(5) defects in antitumor immune responses. This article systematically reviews the remodeling mechanisms of DC subsets across three major metabolic dimensions in the TME: in glucose metabolism, lactate-rich microenvironments suppress MHC class Ⅱ molecule expression via GPR81 signaling, impairing the antigen-presenting capacity of conventional DCs (cDCs); in lipid metabolism, fatty acid oxidation mediated by the Wnt5a-β-catenin-PPARγ-CPT1A axis promotes the polarization of cDCs toward an immunosuppressive phenotype; and in amino acid metabolism, cascade activation of the Arg1-IDO1 pathway induces DCs to acquire a tolerogenic phenotype. In response to these metabolic abnormalities, current intervention strategies have expanded from single-target modulation to multimodal combination approaches, including lipid nanoparticle-based in situ vaccines and mRNA delivery systems, metabolic- immune synergistic blockade, and metabolically optimized DC vaccines. Therefore, deepening the understanding and targeting of DC metabolic checkpoints not only holds promise for reversing the immunosuppressive microenvironment and overcoming therapeutic resistance, but also provides important scientific rationale and translational strategies for developing next-generation metabolic-immune combination therapies.
2026, 33(5):486-493.
DOI: 10.3872/j.issn.1007-385X.2026.05.002
Abstract:
[Abstract] Objective: To investigate the ability of dendritic cell (DC) vaccine loaded with aldehyde dehydrogenase 1A1 (ALDH1A1) mRNA to enhance anti-nasopharyngeal carcinoma stem cell immune responses in vitro. Methods: ALDH1A1 mRNA was transcribed in vitro and electroporated into human peripheral blood-derived DCs to construct ALDH1A1-DC vaccine; EGFP mRNA was used as a transfection control. Flow cytometry was employed to analyze DC phenotypes, lymphocyte subsets, cytotoxic T lymphocyte (CTL) proliferation, and cytokine secretion. ALDH + and ALDH -C666-1 cells were sorted; expression of stem cell markers (CD24, CD133) and stemness-associated genes (OCT4, SOX2, Nanog) was analyzed. The specific cytotoxic capacity induced by ALDH1A1-DC was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Results: EGFP-DC exhibited significantly higher fluorescence expression than untransfected DCs (P < 0.000 1). Moreover, ALDH1A1-DC significantly enhanced the expression of antigen-presenting molecules HLA-ABC, co-stimulatory molecules CD86, CD40, and CCR7 compared to untransfected DCs (P = 0.001 3, P = 0.005 9, P = 0.000 4, P = 0.001 9). Compared with the T lymphocyte group (T) and the DC-T group (DC-induced T lymphocytes), ALDH1A1-DC-induced T lymphocytes (ALDH1A1-DC-T) exhibited the highest proportion of CTL (P < 0.000 1), the highest proliferation index (P = 0.000 2 and P = 0.000 3, respectively), the highest proportions of CD8 +CD69 + cells (P = 0.000 5 and P < 0.000 1, respectively), and the highest proportions of CD8 + IFN-γ + subsets (P = 0.012 6 and P = 0.001 9, respectively). CCK-8 assay demonstrated that ALDH1A1-DC-T exhibited significantly enhanced cytotoxicity against ALDH + C666-1 suspension spheres compared to ALDH - spheres (P = 0.001 0). Furthermore, ALDH1A1-DC-T elicited the most potent anti-ALDH + C666-1 immune response among all lymphocyte groups tested (P = 0.001 0 and · · 486 谢云青, 等. ALDH1A1 mRNA负载树突状细胞疫苗体外诱导抗鼻咽癌干细胞免疫反应 P < 0.000 1, respectively). However, HLA-ABC blockade significantly attenuated this specific cytotoxicity (P < 0.000 1). Conclusion: mRNA transfected into DCs can be translated into protein and promote the maturation of DCs and enhance the ability of DCs to induce specific CTL immune response.
[Abstract] Objective: To investigate the ability of dendritic cell (DC) vaccine loaded with aldehyde dehydrogenase 1A1 (ALDH1A1) mRNA to enhance anti-nasopharyngeal carcinoma stem cell immune responses in vitro. Methods: ALDH1A1 mRNA was transcribed in vitro and electroporated into human peripheral blood-derived DCs to construct ALDH1A1-DC vaccine; EGFP mRNA was used as a transfection control. Flow cytometry was employed to analyze DC phenotypes, lymphocyte subsets, cytotoxic T lymphocyte (CTL) proliferation, and cytokine secretion. ALDH + and ALDH -C666-1 cells were sorted; expression of stem cell markers (CD24, CD133) and stemness-associated genes (OCT4, SOX2, Nanog) was analyzed. The specific cytotoxic capacity induced by ALDH1A1-DC was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Results: EGFP-DC exhibited significantly higher fluorescence expression than untransfected DCs (P < 0.000 1). Moreover, ALDH1A1-DC significantly enhanced the expression of antigen-presenting molecules HLA-ABC, co-stimulatory molecules CD86, CD40, and CCR7 compared to untransfected DCs (P = 0.001 3, P = 0.005 9, P = 0.000 4, P = 0.001 9). Compared with the T lymphocyte group (T) and the DC-T group (DC-induced T lymphocytes), ALDH1A1-DC-induced T lymphocytes (ALDH1A1-DC-T) exhibited the highest proportion of CTL (P < 0.000 1), the highest proliferation index (P = 0.000 2 and P = 0.000 3, respectively), the highest proportions of CD8 +CD69 + cells (P = 0.000 5 and P < 0.000 1, respectively), and the highest proportions of CD8 + IFN-γ + subsets (P = 0.012 6 and P = 0.001 9, respectively). CCK-8 assay demonstrated that ALDH1A1-DC-T exhibited significantly enhanced cytotoxicity against ALDH + C666-1 suspension spheres compared to ALDH - spheres (P = 0.001 0). Furthermore, ALDH1A1-DC-T elicited the most potent anti-ALDH + C666-1 immune response among all lymphocyte groups tested (P = 0.001 0 and · · 486 谢云青, 等. ALDH1A1 mRNA负载树突状细胞疫苗体外诱导抗鼻咽癌干细胞免疫反应 P < 0.000 1, respectively). However, HLA-ABC blockade significantly attenuated this specific cytotoxicity (P < 0.000 1). Conclusion: mRNA transfected into DCs can be translated into protein and promote the maturation of DCs and enhance the ability of DCs to induce specific CTL immune response.
2026, 33(5):494-499.
DOI: 10.3872/j.issn.1007-385X.2026.05.003
Abstract:
[Abstract] Objective: To construct a Trop2-ECD_HPF fusion nanoparticle vaccine and evaluate its immunogenicity and antitumor activity against triple-negative breast cancer (TNBC). Methods: The Trop2-ECD_HPF nanoparticle vaccine was constructed, and subsequently expressed and purified in 293F cells. The purity and homogeneity of the vaccine were verified by size exclusion chromatography and transmission electron microscopy. The vaccine was formulated with aluminum adjuvant and used to immunize female BALB/c mice. The Trop2-specific antibody titers in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the inhibitory effect of the vaccine on the 4T1-Trop2 tumor model was evaluated. Results: The Trop2-ECD_HPF nanoparticles had an average diameter of approximately 20 nm and exhibited high assembly efficiency and high purity. The vaccine effectively induced high- titer Trop2-specific antibodies in mice, with titers reaching 10? at week 6 in the vaccine group, significantly higher than those in the adjuvant control group (P < 0.000 1). In animal studies, mice in the vaccine group exhibited a significant reduction in tumor volume (tumor inhibition rate: 38.6%) and a marked delay in tumor growth rate (P < 0.001), demonstrating strong antitumor efficacy. Conclusion: The Trop2-ECD_HPF fusion nanoparticle vaccine effectively induced a specific humoral immune response and significantly inhibited the growth of TNBC, providing experimental evidence for the development of Trop2-targeted nanoparticle vaccines.
[Abstract] Objective: To construct a Trop2-ECD_HPF fusion nanoparticle vaccine and evaluate its immunogenicity and antitumor activity against triple-negative breast cancer (TNBC). Methods: The Trop2-ECD_HPF nanoparticle vaccine was constructed, and subsequently expressed and purified in 293F cells. The purity and homogeneity of the vaccine were verified by size exclusion chromatography and transmission electron microscopy. The vaccine was formulated with aluminum adjuvant and used to immunize female BALB/c mice. The Trop2-specific antibody titers in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the inhibitory effect of the vaccine on the 4T1-Trop2 tumor model was evaluated. Results: The Trop2-ECD_HPF nanoparticles had an average diameter of approximately 20 nm and exhibited high assembly efficiency and high purity. The vaccine effectively induced high- titer Trop2-specific antibodies in mice, with titers reaching 10? at week 6 in the vaccine group, significantly higher than those in the adjuvant control group (P < 0.000 1). In animal studies, mice in the vaccine group exhibited a significant reduction in tumor volume (tumor inhibition rate: 38.6%) and a marked delay in tumor growth rate (P < 0.001), demonstrating strong antitumor efficacy. Conclusion: The Trop2-ECD_HPF fusion nanoparticle vaccine effectively induced a specific humoral immune response and significantly inhibited the growth of TNBC, providing experimental evidence for the development of Trop2-targeted nanoparticle vaccines.
2026, 33(5):500-509.
DOI: 10.3872/j.issn.1007-385X.2026.05.004
Abstract:
[Abstract] Objective：This study investigated the inhibitory activity and potential mechanism of WAY-312, a small-molecule compound derived through screening of a small-molecule compound library, against the growth and self-renewal capacity of glioblastoma stem cells (GSCs). Methods: Systematic compound screening was conducted on the small molecule compound library through tumor sphere formation assays and cell viability assays; the small molecule inhibitor WAY-302386 (named WAY-312 according to its compound number) obtained through screening was used as the research object. CCK-8 method, Western blot, flow cytometry, and Caspase-Glo 3/7 activity detection method were used to detect the effects of WAY-312 on the proliferation ability, stemness marker expression, cell cycle distribution, and apoptosis level of glioblastoma stem cells at different concentrations. The regulatory effect of WAY-312 on GSC stemness maintenance and self-renewal ability was clarified, and the mechanism of WAY-312 on GSC cell cycle progression and apoptosis was further elucidated. Results: WAY-312 can effectively inhibit the survival of GSCs (P < 0.05); WAY-312 significantly inhibits the number and size of tumor spheroids formed in GSCs (P < 0.05), and treatment with WAY-312 reduces the expression levels of stemness marker proteins SOX2, OLIG2, and BMI1; WAY-312 can effectively inhibit the self-renewal ability of GSCs (P < 0.05); WAY-312 induces GSC cell cycle arrest at the G2/M phase by regulating the expression of cell cycle-related proteins Cyclin B1, CDK4, and CDK6 (P < 0.05); WAY-312 induces apoptosis in GSCs, increases the expression of apoptosis-related proteins cleaved-PARP and BAX, reduces the expression of BCL2, and enhances Caspase-3/7 activity in GSCs after treatment with WAY-312. Conclusion: WAY-312 can inhibit GSC proliferation, stemness maintenance, and self-renewal ability, induce GSC cell cycle arrest at · · 500 车虹宇, 等. 小分子化合物WAY-312通过周期阻滞与凋亡诱导抑制胶质母细胞瘤干细胞增殖及自我更新 G2/M phase, and promote cell apoptosis in a concentration-dependent manner.
[Abstract] Objective：This study investigated the inhibitory activity and potential mechanism of WAY-312, a small-molecule compound derived through screening of a small-molecule compound library, against the growth and self-renewal capacity of glioblastoma stem cells (GSCs). Methods: Systematic compound screening was conducted on the small molecule compound library through tumor sphere formation assays and cell viability assays; the small molecule inhibitor WAY-302386 (named WAY-312 according to its compound number) obtained through screening was used as the research object. CCK-8 method, Western blot, flow cytometry, and Caspase-Glo 3/7 activity detection method were used to detect the effects of WAY-312 on the proliferation ability, stemness marker expression, cell cycle distribution, and apoptosis level of glioblastoma stem cells at different concentrations. The regulatory effect of WAY-312 on GSC stemness maintenance and self-renewal ability was clarified, and the mechanism of WAY-312 on GSC cell cycle progression and apoptosis was further elucidated. Results: WAY-312 can effectively inhibit the survival of GSCs (P < 0.05); WAY-312 significantly inhibits the number and size of tumor spheroids formed in GSCs (P < 0.05), and treatment with WAY-312 reduces the expression levels of stemness marker proteins SOX2, OLIG2, and BMI1; WAY-312 can effectively inhibit the self-renewal ability of GSCs (P < 0.05); WAY-312 induces GSC cell cycle arrest at the G2/M phase by regulating the expression of cell cycle-related proteins Cyclin B1, CDK4, and CDK6 (P < 0.05); WAY-312 induces apoptosis in GSCs, increases the expression of apoptosis-related proteins cleaved-PARP and BAX, reduces the expression of BCL2, and enhances Caspase-3/7 activity in GSCs after treatment with WAY-312. Conclusion: WAY-312 can inhibit GSC proliferation, stemness maintenance, and self-renewal ability, induce GSC cell cycle arrest at · · 500 车虹宇, 等. 小分子化合物WAY-312通过周期阻滞与凋亡诱导抑制胶质母细胞瘤干细胞增殖及自我更新 G2/M phase, and promote cell apoptosis in a concentration-dependent manner.
2026, 33(5):510-520.
DOI: 10.3872/j.issn.1007-385X.2026.05.005
Abstract:
[Abstract] Objective: Esophageal squamous cell carcinoma (ESCC) exhibits pronounced inter- and intra-tumoral heterogeneity, posing substantial challenges for prognostic prediction and therapeutic response evaluation. Cancer stem cells (CSCs) function as pivotal drivers underlying oncogenesis, metastasis, and therapy resistance. In this study, we aim to identify stemness-related molecular subtypes, and construct a subtype classifier to further assist in predicting ESCC patients' therapeutic response. Methods: Twenty-six stem-associated gene sets were retrieved from the StemChecker database. The transcriptome data of 259 ESCC samples from the TCGA-ESCC and GSE53625 databases were quantified using single-sample gene set enrichment analysis. Consensus clustering was then employed to identify stemness subtypes. Subtype-specific differences in prognosis, tumor microenvironment, stemness-related biological process, and therapeutic responses were predicted and analyzed. By applying weighted gene co-expression network analysis (WGCNA), the stemness subtype-related hub genes were identified. Subsequently, the ESCC stemness subtype classifier was constructed and evaluated using three machine learning algorithms: random forest, XGBoost, and the neural network. Results: Based on the single-sample gene set enrichment analysis (ssGSEA) of 26 stemness gene sets, two stemness subtypes (named C1 and C2) were determined, each exhibiting distinct stem-related molecular, immunological and therapeutic characteristics. C2 subtype exhibited adverse prognosis, stronger stemness, higher levels of M2 macrophages and cancer-associated fibroblasts, as well as higher stromal scores. In terms of therapeutic options, immunotherapy might be more appropriate for C1 ESCC patients, while cisplatin, gemcitabine · · 510 郑航, 等. 生物信息学整合机器学习算法鉴定食管鳞状细胞癌干性分子亚型 and docetaxel might be more suitable for C2 ESCC patients. WGCNA identified the blue module in TCGA-ESCC cohort and the black module in GSE53625 cohort as hub gene modules most relevant to the stemness C2 subtype. By integrating the gene sets screened from these two modules, a total of 7 genes were obtained as the final hub genes of the stemness C2 subtype. From the results of the confusion matrix, the validity of the model for predicting stemness subtype using the 7-gene transcriptome data and the machine learning model proposed in this study was proven. The random forest-based stemness classification model achieved higher accuracy, precision and AUC values compared with XGBoost and neural network model. Conclusion: This study delineates valuable perspectives on ESCC stemness heterogeneity, and the developed random forest-based stemness subtype classifier could aid in molecular stratification and personalized therapeutic regimen selection for ESCC patients.
[Abstract] Objective: Esophageal squamous cell carcinoma (ESCC) exhibits pronounced inter- and intra-tumoral heterogeneity, posing substantial challenges for prognostic prediction and therapeutic response evaluation. Cancer stem cells (CSCs) function as pivotal drivers underlying oncogenesis, metastasis, and therapy resistance. In this study, we aim to identify stemness-related molecular subtypes, and construct a subtype classifier to further assist in predicting ESCC patients' therapeutic response. Methods: Twenty-six stem-associated gene sets were retrieved from the StemChecker database. The transcriptome data of 259 ESCC samples from the TCGA-ESCC and GSE53625 databases were quantified using single-sample gene set enrichment analysis. Consensus clustering was then employed to identify stemness subtypes. Subtype-specific differences in prognosis, tumor microenvironment, stemness-related biological process, and therapeutic responses were predicted and analyzed. By applying weighted gene co-expression network analysis (WGCNA), the stemness subtype-related hub genes were identified. Subsequently, the ESCC stemness subtype classifier was constructed and evaluated using three machine learning algorithms: random forest, XGBoost, and the neural network. Results: Based on the single-sample gene set enrichment analysis (ssGSEA) of 26 stemness gene sets, two stemness subtypes (named C1 and C2) were determined, each exhibiting distinct stem-related molecular, immunological and therapeutic characteristics. C2 subtype exhibited adverse prognosis, stronger stemness, higher levels of M2 macrophages and cancer-associated fibroblasts, as well as higher stromal scores. In terms of therapeutic options, immunotherapy might be more appropriate for C1 ESCC patients, while cisplatin, gemcitabine · · 510 郑航, 等. 生物信息学整合机器学习算法鉴定食管鳞状细胞癌干性分子亚型 and docetaxel might be more suitable for C2 ESCC patients. WGCNA identified the blue module in TCGA-ESCC cohort and the black module in GSE53625 cohort as hub gene modules most relevant to the stemness C2 subtype. By integrating the gene sets screened from these two modules, a total of 7 genes were obtained as the final hub genes of the stemness C2 subtype. From the results of the confusion matrix, the validity of the model for predicting stemness subtype using the 7-gene transcriptome data and the machine learning model proposed in this study was proven. The random forest-based stemness classification model achieved higher accuracy, precision and AUC values compared with XGBoost and neural network model. Conclusion: This study delineates valuable perspectives on ESCC stemness heterogeneity, and the developed random forest-based stemness subtype classifier could aid in molecular stratification and personalized therapeutic regimen selection for ESCC patients.
2026, 33(5):521-527.
DOI: 10.3872/j.issn.1007-385X.2026.05.006
Abstract:
[Abstract] Objective：To investigate the therapeutic effect and molecular mechanism of mesenchymal stromal cell-derived extracellular vesicles (MSC-EV) on immune checkpoint inhibitor-related pneumonitis (CIP) in a mouse model. Methods: Foxp3 DTR mice were inoculated with MC38 mouse colon cancer cells and randomly divided into 3 groups (n = 6 per group): ① control group (MC38 inoculation only); ② CIP model group (inoculated with MC38 cells, intraperitoneally injected with diphtheria toxin [DT] and anti-PD-1 antibody); ③ MSC-EV intervention group (based on the CIP model, intranasally administered with MSC-EV [dose 10 9 particles/mouse, every 3 days, 2 times in total]). A mouse CIP model induced by Treg depletion combined with anti-PD-1 antibody was established. In vivo, H-E staining was used to observe lung pathological injury, lung wet/dry ratio was measured to assess pulmonary edema, ELISA was used to detect IL-1β, IL-6, and TNF- α levels in bronchoalveolar lavage fluid (BALF), and flow · · 521 中国肿瘤生物治疗杂志, 2026, 33(5) cytometry was used to detect the proportion of Ly6G ? granulocyte infiltration in BALF. Tumor volume was monitored to evaluate antitumor efficacy. In vitro, DiO fluorescent labeling was used to observe the uptake of extracellular vesicles (EVs) by bone marrow- derived macrophages, and WB assay was used to detect the expression levels of key NLRP3 inflammasome proteins (cleaved GSDMD and mature IL-1β). Potential mechanisms were explored using GEO database miRNA sequencing data (GSE69909), Dicer knockdown, and miR-21/miR-125 inhibitor intervention. Results: Intranasal administration of MSC-EV alleviated lung inflammatory injury in CIP model mice, reduced IL-1β, IL-6, and TNF-α levels and the proportion of Ly6G? granulocyte infiltration in BALF (P < 0.05), without compromising the antitumor efficacy of anti-PD-1 antibody therapy. In vitro DiO labeling tracing showed that MSC-EV could be taken up by macrophages. WB assay showed that MSC-EV decreased the levels of key activated proteins (cleaved GSDMD and mature IL- 1β) of the NLRP3 inflammasome (P < 0.05). In vitro, after Dicer knockdown, the MSC-EV showed a weakened downregulation effect on IL-1β in macrophages (P < 0.05). miRNA sequencing (GEO database, GSE69909) showed high expression of miR-21 and miR-125 in MSC-EV, and inhibition of miR-21 or miR-125 reduced the inhibitory effect of the corresponding MSC-EV on IL-1β cleavage in macrophages (P < 0.05). Conclusion: MSC-EV exert anti-inflammatory effects through their carried miRNAs such as miR-21 and miR- 125, and the mechanism may be related to inhibition of NLRP3 inflammasome activation in macrophages, thereby effectively alleviating CIP without compromising the antitumor efficacy of immune checkpoint inhibitor.
[Abstract] Objective：To investigate the therapeutic effect and molecular mechanism of mesenchymal stromal cell-derived extracellular vesicles (MSC-EV) on immune checkpoint inhibitor-related pneumonitis (CIP) in a mouse model. Methods: Foxp3 DTR mice were inoculated with MC38 mouse colon cancer cells and randomly divided into 3 groups (n = 6 per group): ① control group (MC38 inoculation only); ② CIP model group (inoculated with MC38 cells, intraperitoneally injected with diphtheria toxin [DT] and anti-PD-1 antibody); ③ MSC-EV intervention group (based on the CIP model, intranasally administered with MSC-EV [dose 10 9 particles/mouse, every 3 days, 2 times in total]). A mouse CIP model induced by Treg depletion combined with anti-PD-1 antibody was established. In vivo, H-E staining was used to observe lung pathological injury, lung wet/dry ratio was measured to assess pulmonary edema, ELISA was used to detect IL-1β, IL-6, and TNF- α levels in bronchoalveolar lavage fluid (BALF), and flow · · 521 中国肿瘤生物治疗杂志, 2026, 33(5) cytometry was used to detect the proportion of Ly6G ? granulocyte infiltration in BALF. Tumor volume was monitored to evaluate antitumor efficacy. In vitro, DiO fluorescent labeling was used to observe the uptake of extracellular vesicles (EVs) by bone marrow- derived macrophages, and WB assay was used to detect the expression levels of key NLRP3 inflammasome proteins (cleaved GSDMD and mature IL-1β). Potential mechanisms were explored using GEO database miRNA sequencing data (GSE69909), Dicer knockdown, and miR-21/miR-125 inhibitor intervention. Results: Intranasal administration of MSC-EV alleviated lung inflammatory injury in CIP model mice, reduced IL-1β, IL-6, and TNF-α levels and the proportion of Ly6G? granulocyte infiltration in BALF (P < 0.05), without compromising the antitumor efficacy of anti-PD-1 antibody therapy. In vitro DiO labeling tracing showed that MSC-EV could be taken up by macrophages. WB assay showed that MSC-EV decreased the levels of key activated proteins (cleaved GSDMD and mature IL- 1β) of the NLRP3 inflammasome (P < 0.05). In vitro, after Dicer knockdown, the MSC-EV showed a weakened downregulation effect on IL-1β in macrophages (P < 0.05). miRNA sequencing (GEO database, GSE69909) showed high expression of miR-21 and miR-125 in MSC-EV, and inhibition of miR-21 or miR-125 reduced the inhibitory effect of the corresponding MSC-EV on IL-1β cleavage in macrophages (P < 0.05). Conclusion: MSC-EV exert anti-inflammatory effects through their carried miRNAs such as miR-21 and miR- 125, and the mechanism may be related to inhibition of NLRP3 inflammasome activation in macrophages, thereby effectively alleviating CIP without compromising the antitumor efficacy of immune checkpoint inhibitor.
2026, 33(5):528-536.
DOI: 10.3872/j.issn.1007-385X.2026.05.007
Abstract:
[Abstract] Objective： To investigate the anti-proliferative effect and molecular mechanism of sipeimine on human gastric adenocarcinoma cells (AGS) by modulating the Cyclin D1-mediated CDK4/6-Rb-E2F1 signaling axis. Methods: AGS and GES-1 cells were treated with different concentrations of sipeimine. The optimal inhibitory dose and duration were determined using CCK-8 and crystal violet assays. The effects of sipeimine on AGS cell migration and invasion were assessed via scratch and Transwell assays. Flow cytometry and Western blot analyses evaluated the impact of sipeimine on AGS cell cycle progression and expression of cell cycle- related proteins. Cyclin D1 was overexpressed by plasmid transfection to further elucidate the inhibitory mechanism of sipeimine via WB, crystal violet, scratch, and Transwell assays. An AGS xenograft nude mouse model was established to investigate the in vivo effects and mechanisms of sipeimine, and the expression of Cyclin D1, CDK4, CDK6, Rb, p-Rb, and E2F1 was assessed by immunofluorescence and immunohistochemistry.Results: Compared with the control group, sipeimine at a concentration of 100 μg/mL did not affect the proliferation of GES-1 cells (P > 0.05), but significantly inhibited the proliferation, migration, and invasion capabilities of AGS cells (P < 0.01). It also induced G0/G1 phase arrest in the AGS cell cycle and significantly suppressed the · · 528 刘雪, 等. 西贝素通过调控Cyclin D1介导的CDK4/6-Rb-E2F1信号轴抑制人胃腺癌AGS细胞增殖 expression levels of the cycle-related proteins Cyclin D1, CDK4, CDK6, p-Rb, and E2F1 (P < 0.05 or P < 0.01). Overexpression of Cyclin D1 significantly reduced the inhibitory effect of sipeimine on AGS cells (P < 0.05 or P < 0.01). In tumor-bearing mouse models, sipeimine inhibited AGS xenograft proliferation and affected the expression of Cyclin D1, CDK4, CDK6, p-Rb, and E2F1 in tumor tissues (P < 0.01). Conclusion: Sipeimine may inhibit AGS proliferation by downregulating the Cyclin D1-mediated CDK4/6-Rb-E2F1 signaling pathway activation.
[Abstract] Objective： To investigate the anti-proliferative effect and molecular mechanism of sipeimine on human gastric adenocarcinoma cells (AGS) by modulating the Cyclin D1-mediated CDK4/6-Rb-E2F1 signaling axis. Methods: AGS and GES-1 cells were treated with different concentrations of sipeimine. The optimal inhibitory dose and duration were determined using CCK-8 and crystal violet assays. The effects of sipeimine on AGS cell migration and invasion were assessed via scratch and Transwell assays. Flow cytometry and Western blot analyses evaluated the impact of sipeimine on AGS cell cycle progression and expression of cell cycle- related proteins. Cyclin D1 was overexpressed by plasmid transfection to further elucidate the inhibitory mechanism of sipeimine via WB, crystal violet, scratch, and Transwell assays. An AGS xenograft nude mouse model was established to investigate the in vivo effects and mechanisms of sipeimine, and the expression of Cyclin D1, CDK4, CDK6, Rb, p-Rb, and E2F1 was assessed by immunofluorescence and immunohistochemistry.Results: Compared with the control group, sipeimine at a concentration of 100 μg/mL did not affect the proliferation of GES-1 cells (P > 0.05), but significantly inhibited the proliferation, migration, and invasion capabilities of AGS cells (P < 0.01). It also induced G0/G1 phase arrest in the AGS cell cycle and significantly suppressed the · · 528 刘雪, 等. 西贝素通过调控Cyclin D1介导的CDK4/6-Rb-E2F1信号轴抑制人胃腺癌AGS细胞增殖 expression levels of the cycle-related proteins Cyclin D1, CDK4, CDK6, p-Rb, and E2F1 (P < 0.05 or P < 0.01). Overexpression of Cyclin D1 significantly reduced the inhibitory effect of sipeimine on AGS cells (P < 0.05 or P < 0.01). In tumor-bearing mouse models, sipeimine inhibited AGS xenograft proliferation and affected the expression of Cyclin D1, CDK4, CDK6, p-Rb, and E2F1 in tumor tissues (P < 0.01). Conclusion: Sipeimine may inhibit AGS proliferation by downregulating the Cyclin D1-mediated CDK4/6-Rb-E2F1 signaling pathway activation.
2026, 33(5):537-544.
DOI: 10.3872/j.issn.1007-385X.2026.05.008
Abstract:
[Abstract] Objective： To investigate the role of microRNA-433 (miR-433) in regulating stemness and chemoresistance in colorectal cancer (CRC) cells and to elucidate the underlying molecular regulatory mechanisms. Methods： A 5-FU?resistant HCT?116 cell line was established. The expression levels of miR-433 and stemness markers (SOX2, OCT4, and Nanog) were assessed using RT-qPCR and WB assay. The interaction between miR-433 and its target gene, YAP1, as well as the effect on the subcellular localization of YAP1, were verified through dual-luciferase reporter assays, immunofluorescence staining, and nuclear-cytoplasmic fractionation. Rescue experiments were conducted to confirm the functional role of the miR-433/YAP1 axis. The sensitivity of cells to 5-FU was evaluated using the CCK-8 assay. Results： Compared with parental cells, the expression of miR-433 was significantly downregulated in 5-FU- resistant HCT-116 cells (P < 0.05), whereas the expression of stemness markers (SOX2, OCT4, and Nanog) was upregulated (P < 0.05). Overexpression of miR-433 suppressed the expression of stemness markers, directly targeted YAP1, and inhibited the nuclear translocation of YAP1 (P < 0.05). Restoration of the expression of YAP1 partially reversed the inhibitory effect of miR-433 on stemness · · 537 中国肿瘤生物治疗杂志, 2026, 33(5) molecules (P < 0.05). Functionally, upregulation of miR-433 significantly enhanced the sensitivity of CRC cells to 5-FU; this effect was attenuated by the re-expression of YAP1 (P < 0.05). Conclusion： miR-433 suppresses the stem-like molecular phenotype of colorectal cancer cells and enhances sensitivity to chemotherapeutic agents by directly targeting the YAP1 pathway. The miR-433/YAP1 axis may serve as a potential novel therapeutic target for overcoming chemoresistance in CRC.
[Abstract] Objective： To investigate the role of microRNA-433 (miR-433) in regulating stemness and chemoresistance in colorectal cancer (CRC) cells and to elucidate the underlying molecular regulatory mechanisms. Methods： A 5-FU?resistant HCT?116 cell line was established. The expression levels of miR-433 and stemness markers (SOX2, OCT4, and Nanog) were assessed using RT-qPCR and WB assay. The interaction between miR-433 and its target gene, YAP1, as well as the effect on the subcellular localization of YAP1, were verified through dual-luciferase reporter assays, immunofluorescence staining, and nuclear-cytoplasmic fractionation. Rescue experiments were conducted to confirm the functional role of the miR-433/YAP1 axis. The sensitivity of cells to 5-FU was evaluated using the CCK-8 assay. Results： Compared with parental cells, the expression of miR-433 was significantly downregulated in 5-FU- resistant HCT-116 cells (P < 0.05), whereas the expression of stemness markers (SOX2, OCT4, and Nanog) was upregulated (P < 0.05). Overexpression of miR-433 suppressed the expression of stemness markers, directly targeted YAP1, and inhibited the nuclear translocation of YAP1 (P < 0.05). Restoration of the expression of YAP1 partially reversed the inhibitory effect of miR-433 on stemness · · 537 中国肿瘤生物治疗杂志, 2026, 33(5) molecules (P < 0.05). Functionally, upregulation of miR-433 significantly enhanced the sensitivity of CRC cells to 5-FU; this effect was attenuated by the re-expression of YAP1 (P < 0.05). Conclusion： miR-433 suppresses the stem-like molecular phenotype of colorectal cancer cells and enhances sensitivity to chemotherapeutic agents by directly targeting the YAP1 pathway. The miR-433/YAP1 axis may serve as a potential novel therapeutic target for overcoming chemoresistance in CRC.
2026, 33(5):545-553.
DOI: 10.3872/j.issn.1007-385X.2026.05.009
Abstract:
[Abstract] Objective: To evaluate the predictive and prognostic role of preoperative serum carbohydrate antigen 19-9 (CA19-9) levels in the occurrence of metachronous peritoneal metastasis (mPM) after resection surgery for stage Ⅱ-Ⅲ colorectal cancer. Methods: We retrospectively analyzed clinical and pathological data in stage Ⅱ-Ⅲ colorectal cancer patients treated at Department of Oncology, The First Affiliated Hospital of Shandong First Medical University from January 2019 to January 2024, including preoperative CA19-9 and carcinoembryonic antigen (CEA) levels. Diagnostic performance was evaluated using ROC curves and area under the curve (AUC). Univariate and multivariate logistic regression and Cox proportional hazards models were used to identify risk and prognostic factors, respectively. Using propensity score matching, differences in disease-free survival (DFS) and peritoneal metastasis-free survival (PMFS) between the elevated CA19-9 group and the normal group were compared, and the Log-rank test was used for survival analysis. Results: This study included a total of 286 patients. Elevated preoperative CA19-9 levels were associated with mucinous adenocarcinoma histology (P = 0.005), T4 stage (P < 0.001), lymph node metastasis (P = 0.02), elevated preoperative CEA levels (P = 0.024), nerve invasion (P = 0.02), and poorly differentiated grade (P = 0.045). Elevated CA19-9 levels demonstrated superior predictive accuracy for mPM compared to CEA (AUC: 0.73, 95% CI: 0.61-0.85 vs AUC: 0.64, 95% CI: 0.55-0.73). Multivariate logistic regression analysis revealed that elevated preoperative CA19-9 was an independent predictor of mPM occurrence (OR = 5.59, 95% CI: 2.00-15.58, P = 0.001). Patients with elevated CA19-9 levels had a significantly shorter median DFS (54.27 months vs not reached [NR], HR = 3.55, 95% CI: 1.96-6.44, P < 0.001) and PMFS (NR vs NR, HR = 6.93, 95% CI: 3.25-14.76, P < 0.001) compared to patients with normal · · 545 中国肿瘤生物治疗杂志, 2026, 33(5) CA19-9 levels. After propensity score matching, significant differences in DFS (54.27 months vs NR, HR = 4.26, 95% CI: 1.40-12.98, P = 0.006) and PMFS (NR vs NR, HR = 4.28, 95% CI: 1.19-15.34, P = 0.015) were maintained. Multivariate Cox regression analysis revealed that the elevated preoperative CA19-9 was an independent predictor of poor prognosis for PMFS (HR = 3.70, 95% CI: 1.55- 8.83, P = 0.003). Conclusion: Elevated preoperative serum CA19-9 serves as a sensitive biomarker for postoperative development of mPM in patients with stage Ⅱ-Ⅲ colorectal cancer, providing an independent risk prediction and prognostic stratification.
[Abstract] Objective: To evaluate the predictive and prognostic role of preoperative serum carbohydrate antigen 19-9 (CA19-9) levels in the occurrence of metachronous peritoneal metastasis (mPM) after resection surgery for stage Ⅱ-Ⅲ colorectal cancer. Methods: We retrospectively analyzed clinical and pathological data in stage Ⅱ-Ⅲ colorectal cancer patients treated at Department of Oncology, The First Affiliated Hospital of Shandong First Medical University from January 2019 to January 2024, including preoperative CA19-9 and carcinoembryonic antigen (CEA) levels. Diagnostic performance was evaluated using ROC curves and area under the curve (AUC). Univariate and multivariate logistic regression and Cox proportional hazards models were used to identify risk and prognostic factors, respectively. Using propensity score matching, differences in disease-free survival (DFS) and peritoneal metastasis-free survival (PMFS) between the elevated CA19-9 group and the normal group were compared, and the Log-rank test was used for survival analysis. Results: This study included a total of 286 patients. Elevated preoperative CA19-9 levels were associated with mucinous adenocarcinoma histology (P = 0.005), T4 stage (P < 0.001), lymph node metastasis (P = 0.02), elevated preoperative CEA levels (P = 0.024), nerve invasion (P = 0.02), and poorly differentiated grade (P = 0.045). Elevated CA19-9 levels demonstrated superior predictive accuracy for mPM compared to CEA (AUC: 0.73, 95% CI: 0.61-0.85 vs AUC: 0.64, 95% CI: 0.55-0.73). Multivariate logistic regression analysis revealed that elevated preoperative CA19-9 was an independent predictor of mPM occurrence (OR = 5.59, 95% CI: 2.00-15.58, P = 0.001). Patients with elevated CA19-9 levels had a significantly shorter median DFS (54.27 months vs not reached [NR], HR = 3.55, 95% CI: 1.96-6.44, P < 0.001) and PMFS (NR vs NR, HR = 6.93, 95% CI: 3.25-14.76, P < 0.001) compared to patients with normal · · 545 中国肿瘤生物治疗杂志, 2026, 33(5) CA19-9 levels. After propensity score matching, significant differences in DFS (54.27 months vs NR, HR = 4.26, 95% CI: 1.40-12.98, P = 0.006) and PMFS (NR vs NR, HR = 4.28, 95% CI: 1.19-15.34, P = 0.015) were maintained. Multivariate Cox regression analysis revealed that the elevated preoperative CA19-9 was an independent predictor of poor prognosis for PMFS (HR = 3.70, 95% CI: 1.55- 8.83, P = 0.003). Conclusion: Elevated preoperative serum CA19-9 serves as a sensitive biomarker for postoperative development of mPM in patients with stage Ⅱ-Ⅲ colorectal cancer, providing an independent risk prediction and prognostic stratification.
2026, 33(5):554-562.
DOI: 10.3872/j.issn.1007-385X.2026.05.010
Abstract:
[Abstract] Objective: To investigate the factors influencing pathologic complete response (pCR) following neoadjuvant endocrine therapy in patients with estrogen receptor (ER)-positive breast cancer and to develop and validate a predictive model. Methods: A retrospective study was conducted on 715 patients with ER-positive breast cancer who received neoadjuvant endocrine therapy and surgical treatment at the Fourth Hospital of Hebei Medical University between January 2020 and January 2024. Based on postoperative pathological results, the patients were divided into a pCR group (72 cases) and a non-pCR group (643 cases). The cohort was randomly divided into a training set and a testing set in a 7∶3 ratio, and clinicopathological and laboratory data were collected. Independent risk factors for failure to achieve pCR were identified using univariate and multivariate logistic regression analyses, and a predictive model was constructed. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) for both the training and testing sets. Results: There were no significant differences in clinical data between patients in the training set and the test set. In the training set, there were significant differences between the pCR group and the non-pCR group in terms of the tumor proliferation marker protein Ki-67 index, pre-treatment serum cancer antigen 15-3 (CA15-3) levels, pre-treatment estrogen receptor 1 (ESR1) gene mutation status, pre-treatment miR-1-3p expression levels, pre-treatment SRY-box transcription factor 9 expression levels, clinical stage, and lymph node metastasis (P < · · 554 张华, 等. ER阳性乳腺癌患者新辅助内分泌治疗后疗效影响因素及预测模型构建 0.05). Multivariate logistic regression analysis revealed that the Ki-67 index, pre-treatment serum CA15-3 levels, pre-treatment ESR1 mutation status, pre-treatment miR-1-3p expression levels, and clinical stage were independent influencing factors associated with failure to achieve pCR/non-pCR following neoadjuvant endocrine therapy in patients with ER-positive breast cancer (P < 0.05). A nomogram prediction model was constructed based on these factors, and validation using ROC curves, calibration curves, and DCA confirmed that the model possesses good discriminatory power, predictive accuracy, and clinical utility. Conclusion: The nomogram prediction model incorporating factors such as the Ki-67 index, serum CA15-3 levels, and ESR1 gene mutation status demonstrates good predictive performance for the risk of failing to achieve pCR following neoadjuvant endocrine therapy in patients with ER-positive breast cancer, and can serve as a reference for clinical decision-making.
[Abstract] Objective: To investigate the factors influencing pathologic complete response (pCR) following neoadjuvant endocrine therapy in patients with estrogen receptor (ER)-positive breast cancer and to develop and validate a predictive model. Methods: A retrospective study was conducted on 715 patients with ER-positive breast cancer who received neoadjuvant endocrine therapy and surgical treatment at the Fourth Hospital of Hebei Medical University between January 2020 and January 2024. Based on postoperative pathological results, the patients were divided into a pCR group (72 cases) and a non-pCR group (643 cases). The cohort was randomly divided into a training set and a testing set in a 7∶3 ratio, and clinicopathological and laboratory data were collected. Independent risk factors for failure to achieve pCR were identified using univariate and multivariate logistic regression analyses, and a predictive model was constructed. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) for both the training and testing sets. Results: There were no significant differences in clinical data between patients in the training set and the test set. In the training set, there were significant differences between the pCR group and the non-pCR group in terms of the tumor proliferation marker protein Ki-67 index, pre-treatment serum cancer antigen 15-3 (CA15-3) levels, pre-treatment estrogen receptor 1 (ESR1) gene mutation status, pre-treatment miR-1-3p expression levels, pre-treatment SRY-box transcription factor 9 expression levels, clinical stage, and lymph node metastasis (P < · · 554 张华, 等. ER阳性乳腺癌患者新辅助内分泌治疗后疗效影响因素及预测模型构建 0.05). Multivariate logistic regression analysis revealed that the Ki-67 index, pre-treatment serum CA15-3 levels, pre-treatment ESR1 mutation status, pre-treatment miR-1-3p expression levels, and clinical stage were independent influencing factors associated with failure to achieve pCR/non-pCR following neoadjuvant endocrine therapy in patients with ER-positive breast cancer (P < 0.05). A nomogram prediction model was constructed based on these factors, and validation using ROC curves, calibration curves, and DCA confirmed that the model possesses good discriminatory power, predictive accuracy, and clinical utility. Conclusion: The nomogram prediction model incorporating factors such as the Ki-67 index, serum CA15-3 levels, and ESR1 gene mutation status demonstrates good predictive performance for the risk of failing to achieve pCR following neoadjuvant endocrine therapy in patients with ER-positive breast cancer, and can serve as a reference for clinical decision-making.
2026, 33(5):563-569.
DOI: 10.3872/j.issn.1007-385X.2026.05.011
Abstract:
[Abstract] Objective：To systematically evaluate the efficacy and safety of CD19 CAR-T cell immunotherapy compared with standard treatment in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), and to explore the potential impact of different CAR-T cell products on efficacy through exploratory analysis, so as to provide evidence-based references for clinical treatment decision-making. Methods: Computerized searches were conducted in China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Journal Database, China Biology Medicine Database (SinoMed), PubMed, Embase, and Cochrane Library databases. Randomized controlled trials (RCTs) comparing CD19 CAR-T cell therapy with standard treatment for R/R DLBCL were collected. The search time limit was from the establishment of the databases to October 25, 2025. Two researchers independently conducted literature screening, data extraction, and quality evaluation, and Meta-analysis was performed using R4.2.2 software. Results: A total of 2 phase Ⅲ RCT studies (ZUMA-7, TRANSFORM) were included. Fixed-effect models were selected to merge data · · 563 中国肿瘤生物治疗杂志, 2026, 33(5) for all outcome indicators according to the results of heterogeneity test. In terms of therapeutic effect: CD19 CAR-T cell therapy significantly improved event-free survival (HR = 0.455, 95%CI: 0.363-0.570, P < 0.001) and reduced the risk of death (HR = 0.738, 95%CI: 0.575-0.947, P = 0.017) in patients. At the same time, it could significantly improve the complete response rate (RR = 1.879, 95%CI: 1.574-2.242, P < 0.001). The exploratory analysis by product type showed that both liso-cel and axi-cel were superior to the standard treatment (liso-cel: HR = 0.380, 95% CI: 0.260-0.540, P < 0.001; axi-cel: HR = 0.510, 95%CI: 0.380-0.680, P < 0.001), but this analysis was a comparison between different trials and the evidence level was limited. Safety outcomes showed that the incidence of immune effector cell-related neurotoxicity syndrome (ICANS) with CAR-T cell therapy was significantly increased (RR = 22.387, 95%CI: 4.353-115.132, P < 0.001); the incidence of grade ≥ 3 cytokine release syndrome (CRS) increased (RR = 8.181, 95%CI: 0.935- 71.574, P = 0.058), but the difference was not statistically significant. The overall risk of bias in the included studies was low; sensitivity analysis confirmed the robustness of the results. Conclusion: Based on the results of two RCTs, CD19 CAR-T cells (liso-cel/ axi-cel) can be considered as one of the options for the second-line treatment of R/R DLBCL. Their efficacy is superior to that of standard treatment, and the characteristic adverse reactions (CRS/ICANS) can be controlled after standardized management. CAR-T cell products can be selected individually based on the baseline status of patients. The evidence base of this study is weak, and the above conclusions need to be verified by more high-quality and large-sample RCTs.
[Abstract] Objective：To systematically evaluate the efficacy and safety of CD19 CAR-T cell immunotherapy compared with standard treatment in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), and to explore the potential impact of different CAR-T cell products on efficacy through exploratory analysis, so as to provide evidence-based references for clinical treatment decision-making. Methods: Computerized searches were conducted in China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Journal Database, China Biology Medicine Database (SinoMed), PubMed, Embase, and Cochrane Library databases. Randomized controlled trials (RCTs) comparing CD19 CAR-T cell therapy with standard treatment for R/R DLBCL were collected. The search time limit was from the establishment of the databases to October 25, 2025. Two researchers independently conducted literature screening, data extraction, and quality evaluation, and Meta-analysis was performed using R4.2.2 software. Results: A total of 2 phase Ⅲ RCT studies (ZUMA-7, TRANSFORM) were included. Fixed-effect models were selected to merge data · · 563 中国肿瘤生物治疗杂志, 2026, 33(5) for all outcome indicators according to the results of heterogeneity test. In terms of therapeutic effect: CD19 CAR-T cell therapy significantly improved event-free survival (HR = 0.455, 95%CI: 0.363-0.570, P < 0.001) and reduced the risk of death (HR = 0.738, 95%CI: 0.575-0.947, P = 0.017) in patients. At the same time, it could significantly improve the complete response rate (RR = 1.879, 95%CI: 1.574-2.242, P < 0.001). The exploratory analysis by product type showed that both liso-cel and axi-cel were superior to the standard treatment (liso-cel: HR = 0.380, 95% CI: 0.260-0.540, P < 0.001; axi-cel: HR = 0.510, 95%CI: 0.380-0.680, P < 0.001), but this analysis was a comparison between different trials and the evidence level was limited. Safety outcomes showed that the incidence of immune effector cell-related neurotoxicity syndrome (ICANS) with CAR-T cell therapy was significantly increased (RR = 22.387, 95%CI: 4.353-115.132, P < 0.001); the incidence of grade ≥ 3 cytokine release syndrome (CRS) increased (RR = 8.181, 95%CI: 0.935- 71.574, P = 0.058), but the difference was not statistically significant. The overall risk of bias in the included studies was low; sensitivity analysis confirmed the robustness of the results. Conclusion: Based on the results of two RCTs, CD19 CAR-T cells (liso-cel/ axi-cel) can be considered as one of the options for the second-line treatment of R/R DLBCL. Their efficacy is superior to that of standard treatment, and the characteristic adverse reactions (CRS/ICANS) can be controlled after standardized management. CAR-T cell products can be selected individually based on the baseline status of patients. The evidence base of this study is weak, and the above conclusions need to be verified by more high-quality and large-sample RCTs.
2026, 33(5):570-576.
DOI: 10.3872/j.issn.1007-385X.2026.05.012
Abstract:
[摘 要] IL-2在肿瘤免疫微环境中具有双向调控作用，其能够刺激T淋巴细胞、NK细胞，增强抗肿瘤免疫反应；低水平的IL-2 亦可促进Treg细胞增殖，发挥免疫抑制功能。由于“冷/热”肿瘤对免疫治疗的差异化响应，IL-2与免疫检查点抑制剂（ICI）的联合 应用有望通过促进干细胞样CD8 + T细胞亚群扩增及诱导CXCL9/10的表达，进一步改善冷肿瘤免疫治疗效果。但野生型IL-2在 临床应用中仍面临局限性，为优化IL-2的临床效果，研究者开发氨基酸突变体（MDNA11和H9型等）增强对效应T细胞和NK细 胞的选择性，并减少Treg细胞的激活；PEG 化IL-2（NKTR-214和THOR-707等）通过延长半衰期，减少血管渗漏；抗体复合物 IL-2/S4B6遮蔽IL-2Rα位点，增强对IL-2Rβγ 的偏向激活；融合蛋白（nemvaleukin alfa和IBI363等）通过与免疫分子结合，进一步 增强疗效。综上，工程化IL-2通过优化受体选择性与药代动力学特性，有望克服传统IL-2的临床局限性，为破解ICI耐药性、攻克 “冷肿瘤”治疗壁垒提供新策略。
[摘 要] IL-2在肿瘤免疫微环境中具有双向调控作用，其能够刺激T淋巴细胞、NK细胞，增强抗肿瘤免疫反应；低水平的IL-2 亦可促进Treg细胞增殖，发挥免疫抑制功能。由于“冷/热”肿瘤对免疫治疗的差异化响应，IL-2与免疫检查点抑制剂（ICI）的联合 应用有望通过促进干细胞样CD8 + T细胞亚群扩增及诱导CXCL9/10的表达，进一步改善冷肿瘤免疫治疗效果。但野生型IL-2在 临床应用中仍面临局限性，为优化IL-2的临床效果，研究者开发氨基酸突变体（MDNA11和H9型等）增强对效应T细胞和NK细 胞的选择性，并减少Treg细胞的激活；PEG 化IL-2（NKTR-214和THOR-707等）通过延长半衰期，减少血管渗漏；抗体复合物 IL-2/S4B6遮蔽IL-2Rα位点，增强对IL-2Rβγ 的偏向激活；融合蛋白（nemvaleukin alfa和IBI363等）通过与免疫分子结合，进一步 增强疗效。综上，工程化IL-2通过优化受体选择性与药代动力学特性，有望克服传统IL-2的临床局限性，为破解ICI耐药性、攻克 “冷肿瘤”治疗壁垒提供新策略。
13 Research progress in multimodal treatment strategies for isocitrate dehydrogenase- mutant gliomas
2026, 33(5):577-584.
DOI: 10.3872/j.issn.1007-385X.2026.05.013
Abstract:
[摘 要] 异柠檬酸脱氢酶（IDH）突变型胶质瘤是50岁以下成人最常见的恶性原发性脑肿瘤之一，其患者预后虽优于IDH野生 型患者，但联合治疗伴随的认知毒性限制了该方案的临床应用。本文系统综述IDH突变型胶质瘤免疫机制及治疗进展，IDH突 变产生肿瘤代谢物D-2-羟基戊二酸，进而重塑“代谢-表观遗传-免疫”轴，形成免疫抑制性“冷肿瘤”微环境。基于此，本文系统梳 理了多维度协同治疗策略，从分子分型识别免疫治疗靶点（如HAVCR2、STEAP3），到靶向表观遗传与代谢重编程（如IDH 抑制 剂、组蛋白去乙酰化酶抑制剂），再到临床整合放疗、化疗、手术与靶向治疗形成多模态协同方案，以驱动“冷肿瘤”转变为“热肿 瘤”。尽管面临免疫抑制性微环境相互作用机制不清、联合治疗毒性控制难、生物标志物精准性不足等挑战，未来可通过整合单 细胞多组学、空间转录组学和人工智能等技术解决，为实现精准分型、动态监测和个体化治疗提供依据。
[摘 要] 异柠檬酸脱氢酶（IDH）突变型胶质瘤是50岁以下成人最常见的恶性原发性脑肿瘤之一，其患者预后虽优于IDH野生 型患者，但联合治疗伴随的认知毒性限制了该方案的临床应用。本文系统综述IDH突变型胶质瘤免疫机制及治疗进展，IDH突 变产生肿瘤代谢物D-2-羟基戊二酸，进而重塑“代谢-表观遗传-免疫”轴，形成免疫抑制性“冷肿瘤”微环境。基于此，本文系统梳 理了多维度协同治疗策略，从分子分型识别免疫治疗靶点（如HAVCR2、STEAP3），到靶向表观遗传与代谢重编程（如IDH 抑制 剂、组蛋白去乙酰化酶抑制剂），再到临床整合放疗、化疗、手术与靶向治疗形成多模态协同方案，以驱动“冷肿瘤”转变为“热肿 瘤”。尽管面临免疫抑制性微环境相互作用机制不清、联合治疗毒性控制难、生物标志物精准性不足等挑战，未来可通过整合单 细胞多组学、空间转录组学和人工智能等技术解决，为实现精准分型、动态监测和个体化治疗提供依据。
2026, 33(5):585-588.
DOI: 10.3872/j.issn.1007-385X.2026.05.014
Abstract:
[摘 要] 本文报告1例54岁女性晚期胆道腺癌伴肝转移患者，在接受信迪利单抗联合化疗后出现免疫治疗相关血小板减少症 （ICIIT）。常规升血小板治疗无效后，采用“罗普司亭 + 利妥昔单抗”联合方案成功提升血小板计数。然而，患者首次用药后出现 严重药物性肝损伤（DILI），经停药及保肝治疗后肝功能恢复，最终因癌症进展去世。本案例表明“罗普司亭 + 利妥昔单抗”方案 对ICIIT有效，但存在DILI风险（可能与利妥昔单抗相关），临床应用需严密监测肝功能。
[摘 要] 本文报告1例54岁女性晚期胆道腺癌伴肝转移患者，在接受信迪利单抗联合化疗后出现免疫治疗相关血小板减少症 （ICIIT）。常规升血小板治疗无效后，采用“罗普司亭 + 利妥昔单抗”联合方案成功提升血小板计数。然而，患者首次用药后出现 严重药物性肝损伤（DILI），经停药及保肝治疗后肝功能恢复，最终因癌症进展去世。本案例表明“罗普司亭 + 利妥昔单抗”方案 对ICIIT有效，但存在DILI风险（可能与利妥昔单抗相关），临床应用需严密监测肝功能。
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- 《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
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- 刊号：ISSN 1007-385X
- CN 31-1725/R
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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.