Mobile website
Volume 32,Issue 6,2025 Table of Contents
2025, 32(6):559-569.
DOI: 10.3872/j.issn.1007-385X.2025.06.001
Abstract:
[Abstract] Chimeric antigen receptor gene-modified T (CAR-T) cell therapy represents an immunotherapeutic approach wherein autologous T cells are genetically engineered ex vivo to express specific chimeric antigen receptors (CARs), expanded, and reinfused into patients to specifically recognize and eliminate tumor cells. Despite substantial efficacy in hematological malignancies, CAR-T cell therapy encounters significant barriers in solid tumors. Immune-related adverse events (irAEs), including cytokine release syndrome (CRS), compromise safety profiles, while tumor-associated antigen (TAA) heterogeneity restricts both single-target CAR-T cell applicability and universal CAR-T cell development. Consequently, breakthrough refinements remain essential for clinical translation in solid tumors. This review examines CAR-T cell therapy for solid tumors, critically evaluating safety and universality enhancement strategies through three core approaches: structural CAR design optimization, universal immune receptor retargeting, and antigen universality augmentation. Each approach undergoes systematic analysis of research pathways, advantages, and limitations, with future trajectories delineated. By synthesizing advances in safety and universal design paradigms, the review aims to establish innovative frameworks for CAR-T cell therapeutic development in solid tumor therapeutics.
[Abstract] Chimeric antigen receptor gene-modified T (CAR-T) cell therapy represents an immunotherapeutic approach wherein autologous T cells are genetically engineered ex vivo to express specific chimeric antigen receptors (CARs), expanded, and reinfused into patients to specifically recognize and eliminate tumor cells. Despite substantial efficacy in hematological malignancies, CAR-T cell therapy encounters significant barriers in solid tumors. Immune-related adverse events (irAEs), including cytokine release syndrome (CRS), compromise safety profiles, while tumor-associated antigen (TAA) heterogeneity restricts both single-target CAR-T cell applicability and universal CAR-T cell development. Consequently, breakthrough refinements remain essential for clinical translation in solid tumors. This review examines CAR-T cell therapy for solid tumors, critically evaluating safety and universality enhancement strategies through three core approaches: structural CAR design optimization, universal immune receptor retargeting, and antigen universality augmentation. Each approach undergoes systematic analysis of research pathways, advantages, and limitations, with future trajectories delineated. By synthesizing advances in safety and universal design paradigms, the review aims to establish innovative frameworks for CAR-T cell therapeutic development in solid tumor therapeutics.
2025, 32(6):570-578.
DOI: 10.3872/j.issn.1007-385X.2025.06.002
Abstract:
[Abstract] Objective: To investigate the role of inhibitor of differentiation 2 (Id2) in inducing the generation of central memory T (Tcm) cells and enhancing the anti-tumor persistence of T cells. Methods: CD8+ na?ve T cells were sorted with magnetic beads and then co-cultured with carcinoembryonic antigen (CEA)-loaded dendritic cells (DCs). These cells were induced into effector T (Teff) or Tcm cells by interleukin-2 (IL-2) or IL-7/15/21/23, respectively. The mRNA and protein expression of Id2 and Id3 in T cells were detected using qPCR and WB, respectively. Id2 gene in T cells was knocked down using lentivirus, and the T cell memory phenotype was analyzed by flow cytometry. The expression of PI3K/AKT pathway-related proteins was examined by WB. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were assessed using a Seahorse extracellular flux analyzer. A zebrafish colorectal cancer HCT116 xenograft model was employed to analyze the anti-tumor differences between Teff and Tcm cells. The effect of Id2 gene knockdown in Tcm cells (Tcm-shId2) on the growth inhibition of secondary xenografts was also observed. Results: Tcm cells exhibited high expression of Id3 mRNA (P < 0.05), whereas Teff cells showed high expression of Id2 mRNA (P < 0.001). Tcm cells with Id2 knockdown (Tcm-shId2) were successfully constructed, showing significantly upregulated Id3 expression. Knockdown of Id2 promoted the formation of Tcm cell (P < 0.05). Tcm-shId2 cells underwent metabolic reprogramming via the PI3K/AKT pathway, which effectively suppressed the growth of colorectal cancer xenografts in zebrafish and also produced significant inhibitory effects on secondary tumor growth (P < 0.01). Conclusion: Id2 gene may regulate T cell metabolism through the PI3K/AKT signaling pathway,promoting the differentiation of CD8+ T cells into Tcm cells and effectively inhibiting the growth of colorectal cancer xenografts.
[Abstract] Objective: To investigate the role of inhibitor of differentiation 2 (Id2) in inducing the generation of central memory T (Tcm) cells and enhancing the anti-tumor persistence of T cells. Methods: CD8+ na?ve T cells were sorted with magnetic beads and then co-cultured with carcinoembryonic antigen (CEA)-loaded dendritic cells (DCs). These cells were induced into effector T (Teff) or Tcm cells by interleukin-2 (IL-2) or IL-7/15/21/23, respectively. The mRNA and protein expression of Id2 and Id3 in T cells were detected using qPCR and WB, respectively. Id2 gene in T cells was knocked down using lentivirus, and the T cell memory phenotype was analyzed by flow cytometry. The expression of PI3K/AKT pathway-related proteins was examined by WB. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were assessed using a Seahorse extracellular flux analyzer. A zebrafish colorectal cancer HCT116 xenograft model was employed to analyze the anti-tumor differences between Teff and Tcm cells. The effect of Id2 gene knockdown in Tcm cells (Tcm-shId2) on the growth inhibition of secondary xenografts was also observed. Results: Tcm cells exhibited high expression of Id3 mRNA (P < 0.05), whereas Teff cells showed high expression of Id2 mRNA (P < 0.001). Tcm cells with Id2 knockdown (Tcm-shId2) were successfully constructed, showing significantly upregulated Id3 expression. Knockdown of Id2 promoted the formation of Tcm cell (P < 0.05). Tcm-shId2 cells underwent metabolic reprogramming via the PI3K/AKT pathway, which effectively suppressed the growth of colorectal cancer xenografts in zebrafish and also produced significant inhibitory effects on secondary tumor growth (P < 0.01). Conclusion: Id2 gene may regulate T cell metabolism through the PI3K/AKT signaling pathway,promoting the differentiation of CD8+ T cells into Tcm cells and effectively inhibiting the growth of colorectal cancer xenografts.
2025, 32(6):579-586.
DOI: 10.3872/j.issn.1007-385X.2025.06.003
Abstract:
[Abstract] Objective: To investigate the effects of circular RNA (circRNA) hsa_circ_0081621 on the malignant biological behaviors of human laryngeal squamous cell carcinoma AMC-HN-8 and TU177 cells. Methods: AMC-HN-8 and TU177 cells were routinely cultured. si-NC, si-hsa_circ_0081621, empty vector (vector), and hsa_circ_0081621 overexpression vector (hsa_circ_0081621-OE) were transfected into AMC-HN-8 and TU177 cells, namely si-NC, si-hsa_circ_0081621, vector, and hsa_circ_0081621-OE groups, respectively. The effects of knockdown or overexpression of hsa_circ_0081621 on the proliferation, migration, and invasion of AMC-HN-8 and TU177 cells were detected by CCK-8 assay, colony formation assay, scratch wound healing assay, and Transwell chamber assay. Results: Successful knockdown or overexpression of hsa_circ_0081621 was achieved in AMC-HN-8 and TU177 cells. hsa_circ_0081621 knockdown significantly inhibited while hsa_circ_0081621 overexpression significantly promoted the proliferation, migration, and invasion of AMC-HN-8 and TU177 cells (P < 0.01 or P < 0.001 or P < 0.0001). Conclusion: hsa_circ_0081621 promotes the malignant biological behaviors of human laryngeal squamous cell carcinoma AMC-HN-8 and TU177 cells.
[Abstract] Objective: To investigate the effects of circular RNA (circRNA) hsa_circ_0081621 on the malignant biological behaviors of human laryngeal squamous cell carcinoma AMC-HN-8 and TU177 cells. Methods: AMC-HN-8 and TU177 cells were routinely cultured. si-NC, si-hsa_circ_0081621, empty vector (vector), and hsa_circ_0081621 overexpression vector (hsa_circ_0081621-OE) were transfected into AMC-HN-8 and TU177 cells, namely si-NC, si-hsa_circ_0081621, vector, and hsa_circ_0081621-OE groups, respectively. The effects of knockdown or overexpression of hsa_circ_0081621 on the proliferation, migration, and invasion of AMC-HN-8 and TU177 cells were detected by CCK-8 assay, colony formation assay, scratch wound healing assay, and Transwell chamber assay. Results: Successful knockdown or overexpression of hsa_circ_0081621 was achieved in AMC-HN-8 and TU177 cells. hsa_circ_0081621 knockdown significantly inhibited while hsa_circ_0081621 overexpression significantly promoted the proliferation, migration, and invasion of AMC-HN-8 and TU177 cells (P < 0.01 or P < 0.001 or P < 0.0001). Conclusion: hsa_circ_0081621 promotes the malignant biological behaviors of human laryngeal squamous cell carcinoma AMC-HN-8 and TU177 cells.
2025, 32(6):587-593.
DOI: 10.3872/j.issn.1007-385X.2025.06.004
Abstract:
[Abstract] Objective: To investigate the effects of cyclic adenosine monophosphate response element binding protein (CREB) on the malignant biological behaviors of prostate cancer PC3 cells. Methods: Prostate cancer PC3 cells were routinely cultured. The overexpression control plasmid (vector), CREB overexpression plasmid (CREB-oe), knockdown control sequence (si-NC), and si-CREB sequence were transfected into PC3 cells using transfection reagents, namely vector, CREB-oe, si-NC, and si-CREB groups. Scratch wound healing assay, Transwell chamber assay, and flow cytometry were performed to evaluate cell migration, invasion, and cell cycle distribution, respectively. PC3 cells with CREB knockout were constructed using CRISPR/Cas9 technology, and a xenograft tumor model was employed to evaluate the impact of CREB knockout on tumor growth in vivo. Results: CREB was successfully knocked down or overexpressed in PC3 cells (all P < 0.01). CREB overexpression significantly promoted, while its knockdown significantly inhibited the migration and invasion of PC3 cells (all P < 0.01). Overexpression of CREB promoted the transition of PC3 cells into the S phase, whereas knockdown of CREB induced G1 phase arrest (all P < 0.01). PC3 cells with CREB knockout were successfully constructed, and CREB knockout significantly inhibited the growth of PC3 cell-transplanted tumors (P < 0.01). Conclusion: Knockdown or knockout of CREB inhibits migration and invasion of PC3 cells and induces G1 phase arrest, thereby suppressing tumor growth.
[Abstract] Objective: To investigate the effects of cyclic adenosine monophosphate response element binding protein (CREB) on the malignant biological behaviors of prostate cancer PC3 cells. Methods: Prostate cancer PC3 cells were routinely cultured. The overexpression control plasmid (vector), CREB overexpression plasmid (CREB-oe), knockdown control sequence (si-NC), and si-CREB sequence were transfected into PC3 cells using transfection reagents, namely vector, CREB-oe, si-NC, and si-CREB groups. Scratch wound healing assay, Transwell chamber assay, and flow cytometry were performed to evaluate cell migration, invasion, and cell cycle distribution, respectively. PC3 cells with CREB knockout were constructed using CRISPR/Cas9 technology, and a xenograft tumor model was employed to evaluate the impact of CREB knockout on tumor growth in vivo. Results: CREB was successfully knocked down or overexpressed in PC3 cells (all P < 0.01). CREB overexpression significantly promoted, while its knockdown significantly inhibited the migration and invasion of PC3 cells (all P < 0.01). Overexpression of CREB promoted the transition of PC3 cells into the S phase, whereas knockdown of CREB induced G1 phase arrest (all P < 0.01). PC3 cells with CREB knockout were successfully constructed, and CREB knockout significantly inhibited the growth of PC3 cell-transplanted tumors (P < 0.01). Conclusion: Knockdown or knockout of CREB inhibits migration and invasion of PC3 cells and induces G1 phase arrest, thereby suppressing tumor growth.
2025, 32(6):594-603.
DOI: 10.3872/j.issn.1007-385X.2025.06.005
Abstract:
[Abstract] Objective: To explore the expression of nectin-4 and vanin-1 in esophageal squamous cell carcinoma (ESCC) and its influence on the malignant biological behaviors of ESCC cells, as well as the underlying mechanisms. Methods: Transcriptome sequencing combined with GO and KEGG enrichment analysis was used to identify the downstream target gene (vanin-1) regulated by nectin-4. The mRNA expression of vanin-1 in ESCC tissues was studied using the Timer2.0 database, and the mRNA and protein expression of vanin-1 in normal esophageal epithelial HET-1 and ESCC cells was detected by qPCR and Western blot, identifying ESCC KYSE-410 and KYSE-510 cells with the most significant differential expression. The expression of vanin-1 in KYSE-410 and KYSE-510 cells was knocked down using siRNA. The effects of vanin-1 knockdown on cell proliferation, migration, and invasion were measured using CCK-8 assay, wound healing assay, and Transwell chamber assay. Furthermore, KEGG and GO enrichment analyses were conducted for vanin-1-related signaling pathways. Immunohistochemistry was performed to compare the expression of vanin-1 between ESCC tissues and adjacent non-tumor tissues. Results: Timer2.0 database analysis and qPCR results showed that vanin-1 was highly expressed in both ESCC tissues and cell lines (both P < 0.01). WB assay also confirmed high expression of vanin-1 protein in ESCC cells (P < 0.01). siRNA successfully knocked down vanin-1 expression in KYSE-410 and KYSE-510 cells. Knockdown of vanin-1 significantly inhibited the proliferation, migration, and invasion capabilities of KYSE-410 and KYSE-510 cells (P < 0.05 or P < 0.01 or P < 0.001 or P < 0.000 1). KEGG and GO enrichment analysis suggested that vanin-1 might function through pathways related to pantothenic acid and coenzyme A synthesis metabolism. Immunohistochemistry results indicated that vanin-1 was highly expressed in ESCC tissues (P < 0.000 1). Conclusion: Vanin-1 is highly expressed in ESCC tissues and promotes the proliferation, migration, and invasion of KYSE-410 and KYSE-510 cells through the nectin-4/vanin-1 axis. Targeting vanin-1 might offer a new therapeutic strategy for ESCC.
[Abstract] Objective: To explore the expression of nectin-4 and vanin-1 in esophageal squamous cell carcinoma (ESCC) and its influence on the malignant biological behaviors of ESCC cells, as well as the underlying mechanisms. Methods: Transcriptome sequencing combined with GO and KEGG enrichment analysis was used to identify the downstream target gene (vanin-1) regulated by nectin-4. The mRNA expression of vanin-1 in ESCC tissues was studied using the Timer2.0 database, and the mRNA and protein expression of vanin-1 in normal esophageal epithelial HET-1 and ESCC cells was detected by qPCR and Western blot, identifying ESCC KYSE-410 and KYSE-510 cells with the most significant differential expression. The expression of vanin-1 in KYSE-410 and KYSE-510 cells was knocked down using siRNA. The effects of vanin-1 knockdown on cell proliferation, migration, and invasion were measured using CCK-8 assay, wound healing assay, and Transwell chamber assay. Furthermore, KEGG and GO enrichment analyses were conducted for vanin-1-related signaling pathways. Immunohistochemistry was performed to compare the expression of vanin-1 between ESCC tissues and adjacent non-tumor tissues. Results: Timer2.0 database analysis and qPCR results showed that vanin-1 was highly expressed in both ESCC tissues and cell lines (both P < 0.01). WB assay also confirmed high expression of vanin-1 protein in ESCC cells (P < 0.01). siRNA successfully knocked down vanin-1 expression in KYSE-410 and KYSE-510 cells. Knockdown of vanin-1 significantly inhibited the proliferation, migration, and invasion capabilities of KYSE-410 and KYSE-510 cells (P < 0.05 or P < 0.01 or P < 0.001 or P < 0.000 1). KEGG and GO enrichment analysis suggested that vanin-1 might function through pathways related to pantothenic acid and coenzyme A synthesis metabolism. Immunohistochemistry results indicated that vanin-1 was highly expressed in ESCC tissues (P < 0.000 1). Conclusion: Vanin-1 is highly expressed in ESCC tissues and promotes the proliferation, migration, and invasion of KYSE-410 and KYSE-510 cells through the nectin-4/vanin-1 axis. Targeting vanin-1 might offer a new therapeutic strategy for ESCC.
2025, 32(6):604-610.
DOI: 10.3872/j.issn.1007-385X.2025.06.006
Abstract:
[Abstract] Objective: To investigate the effect of toxifolin (TAX) on the malignant biological behaviors of human bladder cancer T24 cells through the Rac1/NF-κB/AKT signaling pathway. Methods: Bladder cancer T24 cells were routinely cultured and divided into: Ctrl group (untreated), TAX-L group (5 μmol/L TAX), TAX-M group (10 μmol/L TAX), TAX-H group (20 μmol/L TAX), and TAX-H+ Rac1 activator group (20 μmol/L TAX + 50 nmol/L ML-097). CCK-8 method, clone formation assay, scratch healing assay, Transwell chamber assay, and flow cytometry were used to evaluate the effects of different concentrations of TAX on the proliferation, migration, invasion, and apoptosis of T24 cells. WB method was used to examine the expression of apoptosis-related proteins, epithelial mesenchymal transition (EMT)-related proteins, and Rac1/NF-κB/AKT axis related proteins in T24 cells; A nude mice xenograft model was used to assess the effect of TAX on tumor growth. Results: TAX dose-dependently inhibited the proliferation, migration, and invasion of T24 cells and promoted apoptosis (all P < 0.05). TAX also increased the expression of apoptosis proteins BAX and E cadherin, while decreasing the expression of Bcl-2, N-cadherin, and Rac1/NF-κB/AKT signaling pathway-related proteins (all P < 0.05). Furthermore, TAX inhibited tumor growth in the xenograft model (P < 0.05). ML-097 partially reversed these effects (all P < 0.05). Conclusion: TAX inhibits the malignant biological behaviors of bladder cancer T24 cells and promotes their apoptosis by inhibiting Rac1/NF-κB/AKT signaling pathway.
[Abstract] Objective: To investigate the effect of toxifolin (TAX) on the malignant biological behaviors of human bladder cancer T24 cells through the Rac1/NF-κB/AKT signaling pathway. Methods: Bladder cancer T24 cells were routinely cultured and divided into: Ctrl group (untreated), TAX-L group (5 μmol/L TAX), TAX-M group (10 μmol/L TAX), TAX-H group (20 μmol/L TAX), and TAX-H+ Rac1 activator group (20 μmol/L TAX + 50 nmol/L ML-097). CCK-8 method, clone formation assay, scratch healing assay, Transwell chamber assay, and flow cytometry were used to evaluate the effects of different concentrations of TAX on the proliferation, migration, invasion, and apoptosis of T24 cells. WB method was used to examine the expression of apoptosis-related proteins, epithelial mesenchymal transition (EMT)-related proteins, and Rac1/NF-κB/AKT axis related proteins in T24 cells; A nude mice xenograft model was used to assess the effect of TAX on tumor growth. Results: TAX dose-dependently inhibited the proliferation, migration, and invasion of T24 cells and promoted apoptosis (all P < 0.05). TAX also increased the expression of apoptosis proteins BAX and E cadherin, while decreasing the expression of Bcl-2, N-cadherin, and Rac1/NF-κB/AKT signaling pathway-related proteins (all P < 0.05). Furthermore, TAX inhibited tumor growth in the xenograft model (P < 0.05). ML-097 partially reversed these effects (all P < 0.05). Conclusion: TAX inhibits the malignant biological behaviors of bladder cancer T24 cells and promotes their apoptosis by inhibiting Rac1/NF-κB/AKT signaling pathway.
2025, 32(6):611-619.
DOI: 10.3872/j.issn.1007-385X.2025.06.007
Abstract:
[Abstract] Objective: To screen potential comorbid genes shared between inflammatory bowel disease (IBD) and colorectal cancer (CRC), and to explore the relationship between the key gene a disintegrin and metalloprotease 8 (ADAM8) and the pathogenesis of IBD and CRC, as well as the underlying mechanisms. Methods: Transcriptomic data and corresponding clinical information for IBD and CRC were downloaded from the GEO database and TCGA database. Differential expression analysis, prognostic gene screening, and intersection analysis were performed to identify shared genes. Multiple datasets were used to analyze and validate the expression patterns of ADAM8 in IBD and CRC and its correlation with clinicopathological features. Survival analysis was conducted to evaluate the prognostic value of ADAM8 in CRC. Functional and pathway enrichment analyses were conducted to explore the potential mechanisms by which ADAM8 influences CRC progression. The correlation between ADAM8 and tumor microenvironment components was further assessed using tumor microenvironmental algorithms. The database data was validated by detecting the expression in Chinese CRC tissues using immunohistochemistry (IHC). Results: ADAM8 was identified as a potential shared comorbidity gene in IBD and CRC. ADAM8 was significantly upregulated in both IBD and CRC tissues (all P < 0.01), and its high expression was associated with disease progression (P < 0.01). CRC patients with high ADAM8 expression had shorter overall survival (OS) (P < 0.05 or P < 0.01). ADAM8 was also significantly highly expressed in Chinese CRC tissues (P < 0.01). Pathway analysis revealed that ADAM8 expression was closely linked to immune cell migration, cytokine production, and immune receptor interactions. Additionally, ADAM8 expression positively correlated with immune cell infiltration, including neutrophils and macrophages (P < 0.01 or P < 0.001). Conclusion: ADAM8 is highly expressed in IBD and CRC tissues and is closely associated with patient prognosis, disease progression, and immune cell infiltration. It holds promise as a common therapeutic target for both diseases.
[Abstract] Objective: To screen potential comorbid genes shared between inflammatory bowel disease (IBD) and colorectal cancer (CRC), and to explore the relationship between the key gene a disintegrin and metalloprotease 8 (ADAM8) and the pathogenesis of IBD and CRC, as well as the underlying mechanisms. Methods: Transcriptomic data and corresponding clinical information for IBD and CRC were downloaded from the GEO database and TCGA database. Differential expression analysis, prognostic gene screening, and intersection analysis were performed to identify shared genes. Multiple datasets were used to analyze and validate the expression patterns of ADAM8 in IBD and CRC and its correlation with clinicopathological features. Survival analysis was conducted to evaluate the prognostic value of ADAM8 in CRC. Functional and pathway enrichment analyses were conducted to explore the potential mechanisms by which ADAM8 influences CRC progression. The correlation between ADAM8 and tumor microenvironment components was further assessed using tumor microenvironmental algorithms. The database data was validated by detecting the expression in Chinese CRC tissues using immunohistochemistry (IHC). Results: ADAM8 was identified as a potential shared comorbidity gene in IBD and CRC. ADAM8 was significantly upregulated in both IBD and CRC tissues (all P < 0.01), and its high expression was associated with disease progression (P < 0.01). CRC patients with high ADAM8 expression had shorter overall survival (OS) (P < 0.05 or P < 0.01). ADAM8 was also significantly highly expressed in Chinese CRC tissues (P < 0.01). Pathway analysis revealed that ADAM8 expression was closely linked to immune cell migration, cytokine production, and immune receptor interactions. Additionally, ADAM8 expression positively correlated with immune cell infiltration, including neutrophils and macrophages (P < 0.01 or P < 0.001). Conclusion: ADAM8 is highly expressed in IBD and CRC tissues and is closely associated with patient prognosis, disease progression, and immune cell infiltration. It holds promise as a common therapeutic target for both diseases.
2025, 32(6):620-627.
DOI: 10.3872/j.issn.1007-385X.2025.06.008
Abstract:
[Abstract] Objective: To investigate the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in different types of breast cancer tissues and its relationship with patient prognosis and immune cell infiltration. Methods: RNA sequencing data of breast cancer and corresponding clinical information from the TCGA database were collected. The differential expression of IDO1 mRNA in various breast cancer tissues (different subtypes, stages, menopause statuses, and age groups) and adjacent normal tissues were analyzed. Breast cancer patients with significant differences in IDO1 mRNA expression were divided into high and low expression groups, and their disease-specific survival (DSS) was compared between the two groups. The relationship between IDO1 mRNA expression and immune cell infiltration in cancer tissues with significant DSS differences was analyzed. Immunohistochemistry was used to detect IDO1 protein expression in ER-negative, PR-negative, HER2-positive, and stage Ⅱ breast cancer tissues, to verify the data from the database. Results: IDO1 mRNA was highly expressed in breast cancer tissues but varied across different breast cancer types. IDO1 mRNA was highly expressed in breast cancer tissues of patients with ER-negative, PR-negative, HER2-positive, HER2-negative subtypes, stage Ⅱ, T2 stage, N0 stage, M0 stage, premenopausal, postmenopausal, and age ≤ 60 years (P < 0.05 or P < 0.01, or P < 0.001). In the ER negative, PR-negative, HER2-positive, and stage Ⅱ subgroups, breast cancer tissues patients with high IDO1 mRNA expression had significantly higher DSS than those with low expression (P < 0.05 or P < 0.01). In ER-negative, PR-negative, HER2-positive, and stage Ⅱ breast cancer tissues, IDO1 mRNA expression was associated with immune cell infiltration, including activated dendritic cells (aDCs), Th1 cells, T cells, CD56dim NK cells, CTLs, and Treg cells (all P < 0.001). IDO1 protein was highly expressed in ER-negative, PR-negative, HER2-positive, and stage Ⅱ breast cancer tissues (all P < 0.001), consistent with the data from the database. Conclusion: IDO1 expression varies across different types of breast cancer tissues. The expression of IDO1 is associated with the prognosis and immune cell infiltration in ER-negative, PR-negative, HER2-positive, and at stage Ⅱ breast cancer patients.
[Abstract] Objective: To investigate the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in different types of breast cancer tissues and its relationship with patient prognosis and immune cell infiltration. Methods: RNA sequencing data of breast cancer and corresponding clinical information from the TCGA database were collected. The differential expression of IDO1 mRNA in various breast cancer tissues (different subtypes, stages, menopause statuses, and age groups) and adjacent normal tissues were analyzed. Breast cancer patients with significant differences in IDO1 mRNA expression were divided into high and low expression groups, and their disease-specific survival (DSS) was compared between the two groups. The relationship between IDO1 mRNA expression and immune cell infiltration in cancer tissues with significant DSS differences was analyzed. Immunohistochemistry was used to detect IDO1 protein expression in ER-negative, PR-negative, HER2-positive, and stage Ⅱ breast cancer tissues, to verify the data from the database. Results: IDO1 mRNA was highly expressed in breast cancer tissues but varied across different breast cancer types. IDO1 mRNA was highly expressed in breast cancer tissues of patients with ER-negative, PR-negative, HER2-positive, HER2-negative subtypes, stage Ⅱ, T2 stage, N0 stage, M0 stage, premenopausal, postmenopausal, and age ≤ 60 years (P < 0.05 or P < 0.01, or P < 0.001). In the ER negative, PR-negative, HER2-positive, and stage Ⅱ subgroups, breast cancer tissues patients with high IDO1 mRNA expression had significantly higher DSS than those with low expression (P < 0.05 or P < 0.01). In ER-negative, PR-negative, HER2-positive, and stage Ⅱ breast cancer tissues, IDO1 mRNA expression was associated with immune cell infiltration, including activated dendritic cells (aDCs), Th1 cells, T cells, CD56dim NK cells, CTLs, and Treg cells (all P < 0.001). IDO1 protein was highly expressed in ER-negative, PR-negative, HER2-positive, and stage Ⅱ breast cancer tissues (all P < 0.001), consistent with the data from the database. Conclusion: IDO1 expression varies across different types of breast cancer tissues. The expression of IDO1 is associated with the prognosis and immune cell infiltration in ER-negative, PR-negative, HER2-positive, and at stage Ⅱ breast cancer patients.
FAN Yunxia
,
GAO Jun
,
HAN Zhihai
,
HUANG Bingqiao
,
QI Bing
,
CHEN Yinjiashu
,
XI Feng
,
WANG Dan
,
NIAN Peipei
,
FAN Weijun
2025, 32(6):628-635.
DOI: 10.3872/j.issn.1007-385X.2025.06.009
Abstract:
[Abstract] Objective: To preliminarily investigate the safety and efficacy of programmed death-1 (PD-1) inhibitor combined with cord blood-derived natural killer cells (NK cells) in the treatment of advanced malignant solid tumors in an exploratory clinical trial. Methods: Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi 'an Medical University from December 2019 to December 2021 were enrolled. According to tumor type and CSCO guidelines, patients received multiple treatment cycles (21 days per cycle) consisting of standard chemotherapy, targeted therapy, or bevacizumab combined with PD-1 inhibitor. Umbilical cord blood-derived NK cells (8 × 107 cells per infusion) were infused at appropriate intervals during the treatment course. Target lesion size, tumor markers, levels of 12 peripheral blood cytokines, and lymphocyte subsets were assessed in each treatment cycle. Adverse events were also monitored throughout the treatment. Results: Following the treatment with PD-1 inhibitor combined with cord blood NK cells, 2 patients achieved stable disease (SD, per RECIST 1.1 criteria), with durations of 118 days and 92 days, respectively. After NK cell infusion, patient #1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods; patient #2 showed significant reductions in tumor markers CA199, CA242, and CA724. Conclusion: The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors. No severe immune-related adverse reactions were observed in the three patients enrolled in this study.
[Abstract] Objective: To preliminarily investigate the safety and efficacy of programmed death-1 (PD-1) inhibitor combined with cord blood-derived natural killer cells (NK cells) in the treatment of advanced malignant solid tumors in an exploratory clinical trial. Methods: Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi 'an Medical University from December 2019 to December 2021 were enrolled. According to tumor type and CSCO guidelines, patients received multiple treatment cycles (21 days per cycle) consisting of standard chemotherapy, targeted therapy, or bevacizumab combined with PD-1 inhibitor. Umbilical cord blood-derived NK cells (8 × 107 cells per infusion) were infused at appropriate intervals during the treatment course. Target lesion size, tumor markers, levels of 12 peripheral blood cytokines, and lymphocyte subsets were assessed in each treatment cycle. Adverse events were also monitored throughout the treatment. Results: Following the treatment with PD-1 inhibitor combined with cord blood NK cells, 2 patients achieved stable disease (SD, per RECIST 1.1 criteria), with durations of 118 days and 92 days, respectively. After NK cell infusion, patient #1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods; patient #2 showed significant reductions in tumor markers CA199, CA242, and CA724. Conclusion: The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors. No severe immune-related adverse reactions were observed in the three patients enrolled in this study.
2025, 32(6):636-640.
DOI: 10.3872/j.issn.1007-385X.2025.06.010
Abstract:
[Abstract] Objective: To explore the expression of filaggrin (FLG) in melanoma tissues and its correlation with clinicopathological features and prognosis in patients. Methods: A total of 70 melanoma patients treated at the People’ s Hospital Affiliated to Shandong First Medical University from June 2019 to August 2020 were selected as research subjects. Tumor tissues and adjacent tissues obtained during surgery were examined for FLG expression using immunohistochemistry. Based on FLG expression, patients were divided into a positive group and a negative group. The positive expression rates of FLG in tumor tissues, adjacent tissues and melanoma tissues with different pathological features were compared. The patients were followed up for 3 years, and based on prognosis, they were divided into a survival group (n = 43) and a death group (n = 27). The FLG positive expression rates were compared between the two groups. Kaplan-Meier survival curves were plotted, and survival times were compared. Results: The positive FLG expression rate in melanoma tissues was significantly lower than that in adjacent tissues (P < 0.05). The proportions of patients with tumor diameter > 1 cm, Breslow thickness > 2 mm, local ulcer, TNM stage Ⅲ-Ⅳ, lymph node metastasis, and tumor invasion in positive FLG expression group were significantly lower than those in negative group (P < 0.05 or P < 0.01). Among the 70 patients, 27 cases died and 43 survived, with a survival rate of 61.42%. The positive FLG expression rate was significantly lower in death group than that in survival group (P < 0.05). The survival time of FLG-positive patients was significantly longer than that of FLG-negative patients (P = 0.010). Multivariate Cox regression analysis revealed that Breslow thickness > 2 mm, TNM grade Ⅲ-Ⅳ, lymph node metastasis, and tumor invasion were risk factors for the prognosis of melanoma patients (P < 0.01 or P < 0.001), while positive FLG expression was a protective factor (P < 0.01 or P < 0.001). Conclusion: FLG expression is significantly decreased in melanoma tissues and is associated with pathological features such as Breslow thickness, tumor stage, invasion, lymph node metastasis, and prognosis.
[Abstract] Objective: To explore the expression of filaggrin (FLG) in melanoma tissues and its correlation with clinicopathological features and prognosis in patients. Methods: A total of 70 melanoma patients treated at the People’ s Hospital Affiliated to Shandong First Medical University from June 2019 to August 2020 were selected as research subjects. Tumor tissues and adjacent tissues obtained during surgery were examined for FLG expression using immunohistochemistry. Based on FLG expression, patients were divided into a positive group and a negative group. The positive expression rates of FLG in tumor tissues, adjacent tissues and melanoma tissues with different pathological features were compared. The patients were followed up for 3 years, and based on prognosis, they were divided into a survival group (n = 43) and a death group (n = 27). The FLG positive expression rates were compared between the two groups. Kaplan-Meier survival curves were plotted, and survival times were compared. Results: The positive FLG expression rate in melanoma tissues was significantly lower than that in adjacent tissues (P < 0.05). The proportions of patients with tumor diameter > 1 cm, Breslow thickness > 2 mm, local ulcer, TNM stage Ⅲ-Ⅳ, lymph node metastasis, and tumor invasion in positive FLG expression group were significantly lower than those in negative group (P < 0.05 or P < 0.01). Among the 70 patients, 27 cases died and 43 survived, with a survival rate of 61.42%. The positive FLG expression rate was significantly lower in death group than that in survival group (P < 0.05). The survival time of FLG-positive patients was significantly longer than that of FLG-negative patients (P = 0.010). Multivariate Cox regression analysis revealed that Breslow thickness > 2 mm, TNM grade Ⅲ-Ⅳ, lymph node metastasis, and tumor invasion were risk factors for the prognosis of melanoma patients (P < 0.01 or P < 0.001), while positive FLG expression was a protective factor (P < 0.01 or P < 0.001). Conclusion: FLG expression is significantly decreased in melanoma tissues and is associated with pathological features such as Breslow thickness, tumor stage, invasion, lymph node metastasis, and prognosis.
2025, 32(6):641-648.
DOI: 10.3872/j.issn.1007-385X.2025.06.011
Abstract:
[Abstract] Objective: To investigate the expression of mismatch repair protein 2 (MSH2) in gastric cancer and its correlation with patient clinical characteristics, as well as its effects on malignant biological behaviors of gastric cancer cells and underlying mechanisms. Methods: Tumor tissues and matched adjacent tissues were collected from 40 gastric cancer patients admitted to Xingtai People's Hospital from May 2020 to July 2022, along with patient clinical data. Normal gastric mucosal epithelial cells (GES-1) and gastric cancer cell lines (AGS, MKN45, and BGC-823) were routinely cultured. The sh-NC (negative control), shMSH2-1, and shMSH2-2 lentiviral vectors were transfected into AGS and MKN45 cells, respectively, dividing the cells into sh-NC, shMSH2-1, and shMSH2-2 groups accordingly. The proliferation, migration, and invasion capabilities of AGS and MKN45 cells in each group were assessed using CCK-8 assay, colony formation assay, Edu staining, and Transwell chamber assay, respectively. A nude mouse MKN45 cell xenograft model was established to evaluate the effect of MSH2 knockdown on tumor growth. WB was performed to detect the expression of MSH2, PI3K/AKT/mTOR pathway-related proteins, and epithelial-mesenchymal transition (EMT) -related proteins in cells and xenograft tissues. Results: MSH2 was highly expressed in gastric cancer tissues and cell lines, and this elevated expression was associated with lymph node metastasis, advanced T stage, and poor histological differentiation (all P < 0.001). Successful knockdown of MSH2 expression was achieved in AGS and MKN45 cells (P < 0.001). MSH2 knockdown significantly inhibited cell viability, Edu-positive cell ratio, colony formation, migration, and invasion ability of AGS and MKN45 cells (all P < 0.001), as well as xenograft tumor growth (P < 0.001). It markedly suppressed the expression of MSH2 protein, PI3K/AKT/mTOR pathway-related proteins, and N-cadherin protein (all P < 0.001), while promoting E-cadherin expression (P < 0.001) in both AGS, MKN45 cells and MKN45 xenograft tissues. Conclusion: MSH2 is highly expressed in gastric cancer tissues and cell lines and is associated with lymph node metastasis, advanced T-stage progression, and poor histological differentiation. Knockdown of MSH2 expression suppresses the malignant biological behaviors of AGS and MKN45 cells by inhibiting the PI3K/AKT/mTOR pathway, positioning MSH2 as a potential therapeutic target for gastric cancer management.
[Abstract] Objective: To investigate the expression of mismatch repair protein 2 (MSH2) in gastric cancer and its correlation with patient clinical characteristics, as well as its effects on malignant biological behaviors of gastric cancer cells and underlying mechanisms. Methods: Tumor tissues and matched adjacent tissues were collected from 40 gastric cancer patients admitted to Xingtai People's Hospital from May 2020 to July 2022, along with patient clinical data. Normal gastric mucosal epithelial cells (GES-1) and gastric cancer cell lines (AGS, MKN45, and BGC-823) were routinely cultured. The sh-NC (negative control), shMSH2-1, and shMSH2-2 lentiviral vectors were transfected into AGS and MKN45 cells, respectively, dividing the cells into sh-NC, shMSH2-1, and shMSH2-2 groups accordingly. The proliferation, migration, and invasion capabilities of AGS and MKN45 cells in each group were assessed using CCK-8 assay, colony formation assay, Edu staining, and Transwell chamber assay, respectively. A nude mouse MKN45 cell xenograft model was established to evaluate the effect of MSH2 knockdown on tumor growth. WB was performed to detect the expression of MSH2, PI3K/AKT/mTOR pathway-related proteins, and epithelial-mesenchymal transition (EMT) -related proteins in cells and xenograft tissues. Results: MSH2 was highly expressed in gastric cancer tissues and cell lines, and this elevated expression was associated with lymph node metastasis, advanced T stage, and poor histological differentiation (all P < 0.001). Successful knockdown of MSH2 expression was achieved in AGS and MKN45 cells (P < 0.001). MSH2 knockdown significantly inhibited cell viability, Edu-positive cell ratio, colony formation, migration, and invasion ability of AGS and MKN45 cells (all P < 0.001), as well as xenograft tumor growth (P < 0.001). It markedly suppressed the expression of MSH2 protein, PI3K/AKT/mTOR pathway-related proteins, and N-cadherin protein (all P < 0.001), while promoting E-cadherin expression (P < 0.001) in both AGS, MKN45 cells and MKN45 xenograft tissues. Conclusion: MSH2 is highly expressed in gastric cancer tissues and cell lines and is associated with lymph node metastasis, advanced T-stage progression, and poor histological differentiation. Knockdown of MSH2 expression suppresses the malignant biological behaviors of AGS and MKN45 cells by inhibiting the PI3K/AKT/mTOR pathway, positioning MSH2 as a potential therapeutic target for gastric cancer management.
2025, 32(6):649-657.
DOI: 10.3872/j.issn.1007-385X.2025.06.012
Abstract:
[摘 要] 近年来，随着中国居民膳食结构西方化及人口老龄化，中国结直肠癌（CRC）的发病率和病死率总体上均有所增加。 CRC是一种多因素引起的疾病，肠道菌群失调贯穿其发展过程。目前，针对CRC的抗肿瘤药物研发与创新取得了显著的进展， 然而其药物应答率仍然有限，部分患者及转移性CRC患者的常规标准治疗效果并不理想且预后极差，因此，亟需寻求更加个体化 的治疗方案。当前的研究已将CRC与肠道菌群联系起来，一些临床证据也强调了肠道菌群在CRC治疗中的潜力——靶向干预 致病菌株及其相关信号通路，正逐渐被认为可能成为治疗CRC的一种独特而有效的方法。因此，基于肠道菌群的创新治疗策略 有望成为继放化疗、靶向化疗和免疫治疗后的新兴辅助治疗手段。本文将深入探讨肠道菌群与CRC之间的复杂相互作用，并对 新兴干预措施，如粪菌移植、二代益生菌及微生态调节剂进行系统性概述，以期为CRC的临床预防和治疗提供新的理论依据和实 践指导。
[摘 要] 近年来，随着中国居民膳食结构西方化及人口老龄化，中国结直肠癌（CRC）的发病率和病死率总体上均有所增加。 CRC是一种多因素引起的疾病，肠道菌群失调贯穿其发展过程。目前，针对CRC的抗肿瘤药物研发与创新取得了显著的进展， 然而其药物应答率仍然有限，部分患者及转移性CRC患者的常规标准治疗效果并不理想且预后极差，因此，亟需寻求更加个体化 的治疗方案。当前的研究已将CRC与肠道菌群联系起来，一些临床证据也强调了肠道菌群在CRC治疗中的潜力——靶向干预 致病菌株及其相关信号通路，正逐渐被认为可能成为治疗CRC的一种独特而有效的方法。因此，基于肠道菌群的创新治疗策略 有望成为继放化疗、靶向化疗和免疫治疗后的新兴辅助治疗手段。本文将深入探讨肠道菌群与CRC之间的复杂相互作用，并对 新兴干预措施，如粪菌移植、二代益生菌及微生态调节剂进行系统性概述，以期为CRC的临床预防和治疗提供新的理论依据和实 践指导。
2025, 32(6):658-663.
DOI: 10.3872/j.issn.1007-385X.2025.06.013
Abstract:
[摘 要] 传统的癌症治疗方法存在诸多局限性，难以实现肿瘤的精准治疗与长期控制。声动力治疗（SDT）作为一种非侵入 性、时空精准且具有深度组织穿透性的新兴肿瘤治疗手段，能够通过低强度超声波激活在肿瘤部位富集的声敏感剂，从而生成活 性氧物质，选择性地杀死肿瘤细胞，且对正常组织损伤较小。在精准杀伤肿瘤细胞的同时，SDT还能诱导癌细胞发生免疫原性细 胞死亡，激活免疫细胞的抗肿瘤活性，启动抗原特异性免疫反应。然而，由于复杂的免疫抑制性肿瘤微环境，SDT单独应用时产 生的免疫效应有限，难以有效抑制肿瘤的复发和远处转移。近年来，研究者们尝试将SDT与免疫治疗联合应用，这种联合疗法通 过其协同机制增强了抗肿瘤免疫效应，同时减少了免疫治疗所产生的脱靶毒性，已成为一种突破现有治疗局限的新型治疗策略。 本综述将探讨SDT的作用机制、其引发的免疫效应、以及SDT与免疫治疗的多种联合模式，并对当前的研究进展和面临的挑战进 行总结和展望。
[摘 要] 传统的癌症治疗方法存在诸多局限性，难以实现肿瘤的精准治疗与长期控制。声动力治疗（SDT）作为一种非侵入 性、时空精准且具有深度组织穿透性的新兴肿瘤治疗手段，能够通过低强度超声波激活在肿瘤部位富集的声敏感剂，从而生成活 性氧物质，选择性地杀死肿瘤细胞，且对正常组织损伤较小。在精准杀伤肿瘤细胞的同时，SDT还能诱导癌细胞发生免疫原性细 胞死亡，激活免疫细胞的抗肿瘤活性，启动抗原特异性免疫反应。然而，由于复杂的免疫抑制性肿瘤微环境，SDT单独应用时产 生的免疫效应有限，难以有效抑制肿瘤的复发和远处转移。近年来，研究者们尝试将SDT与免疫治疗联合应用，这种联合疗法通 过其协同机制增强了抗肿瘤免疫效应，同时减少了免疫治疗所产生的脱靶毒性，已成为一种突破现有治疗局限的新型治疗策略。 本综述将探讨SDT的作用机制、其引发的免疫效应、以及SDT与免疫治疗的多种联合模式，并对当前的研究进展和面临的挑战进 行总结和展望。
2025, 32(6):664-669.
DOI: 10.3872/j.issn.1007-385X.2025.06.014
Abstract:
[摘 要] 肺癌是全球恶性肿瘤相关死亡的首位病因。Janus激酶（JAK）2/信号转导和转录激活因子（STAT）3信号通路在肺癌 中通过复杂的上下游信号被异常激活并显著高表达，利用多重机制促进肺癌细胞的增殖、迁移、抗凋亡及肿瘤血管生成等恶性生 物学行为，从而导致患者病情进展及不良预后。借由对JAK2/STAT3信号通路上游靶基因表达水平上的调控，或是直接靶向作用 于通路传导过程中的关键原件，可抑制或调控通路的持续性激活和异常信号转导从而改善肺癌的恶性生物学行为。本文着重介 绍了JAK2/STAT3信号通路在肺癌中的作用与潜在治疗意义，同时论述了目前基于JAK2/STAT3信号通路设计出来的多种干预 靶点药物及其未来的前景，为临床治疗肺癌提供新思路。
[摘 要] 肺癌是全球恶性肿瘤相关死亡的首位病因。Janus激酶（JAK）2/信号转导和转录激活因子（STAT）3信号通路在肺癌 中通过复杂的上下游信号被异常激活并显著高表达，利用多重机制促进肺癌细胞的增殖、迁移、抗凋亡及肿瘤血管生成等恶性生 物学行为，从而导致患者病情进展及不良预后。借由对JAK2/STAT3信号通路上游靶基因表达水平上的调控，或是直接靶向作用 于通路传导过程中的关键原件，可抑制或调控通路的持续性激活和异常信号转导从而改善肺癌的恶性生物学行为。本文着重介 绍了JAK2/STAT3信号通路在肺癌中的作用与潜在治疗意义，同时论述了目前基于JAK2/STAT3信号通路设计出来的多种干预 靶点药物及其未来的前景，为临床治疗肺癌提供新思路。
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
您是第位访问者
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.