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Volume 33,Issue 6,2026 Table of Contents
2026, 33(6):589-601.
DOI: 10.3872/j.issn.1007-385X.2026.06.001
Abstract:
[Abstract] Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive, often diagnosed at late stages, and generally shows limited response to systemic therapies. The dense fibrotic stroma, abnormal vasculature, and immunosuppressive tumor microenvironment collectively impair drug penetration and contribute to the "cold tumor" phenotype, significantly limiting therapeutic efficacy. Mesenchymal stromal cells (MSCs), known for their inflammatory-directed migration, immune modulation, and paracrine effects, can serve as living delivery vehicles to selectively deliver cytokines, chemotherapeutic agents, oncolytic viruses, and suicide genes to tumor sites, offering promising strategies to overcome stromal barriers and reshape the tumor microenvironment. However, MSCs exhibit significant plasticity in the tumor context, displaying a "double-edged sword" effect, potentially being reprogrammed by the tumor microenvironment to exert immunosuppressive, pro-angiogenic, pro-fibrotic, pro-invasive, and drug-resistance-supporting activities. Moreover, the in vivo distribution and payload release of MSCs lack quantifiable and controllable evidence, while inconsistent manufacturing processes and functional quality control standards hinder clinical translation. This review focuses on the mechanisms underlying MSC-tumor microenvironment interactions and recent advances in engineered MSC-based delivery of therapeutic proteins, drugs, oncolytic viruses, and suicide genes, with particular emphasis on challenges related to safety, efficacy evaluation, and quality control. Developing programmable MSC platforms with microenvironment-responsive release and safety switches, establishing functional evaluation or release criteria for tumor therapy, and advancing cell-free approaches such as MSC-derived extracellular vesicles may enhance reproducibility and reduce risks associated with long-term persistence in vivo.
[Abstract] Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive, often diagnosed at late stages, and generally shows limited response to systemic therapies. The dense fibrotic stroma, abnormal vasculature, and immunosuppressive tumor microenvironment collectively impair drug penetration and contribute to the "cold tumor" phenotype, significantly limiting therapeutic efficacy. Mesenchymal stromal cells (MSCs), known for their inflammatory-directed migration, immune modulation, and paracrine effects, can serve as living delivery vehicles to selectively deliver cytokines, chemotherapeutic agents, oncolytic viruses, and suicide genes to tumor sites, offering promising strategies to overcome stromal barriers and reshape the tumor microenvironment. However, MSCs exhibit significant plasticity in the tumor context, displaying a "double-edged sword" effect, potentially being reprogrammed by the tumor microenvironment to exert immunosuppressive, pro-angiogenic, pro-fibrotic, pro-invasive, and drug-resistance-supporting activities. Moreover, the in vivo distribution and payload release of MSCs lack quantifiable and controllable evidence, while inconsistent manufacturing processes and functional quality control standards hinder clinical translation. This review focuses on the mechanisms underlying MSC-tumor microenvironment interactions and recent advances in engineered MSC-based delivery of therapeutic proteins, drugs, oncolytic viruses, and suicide genes, with particular emphasis on challenges related to safety, efficacy evaluation, and quality control. Developing programmable MSC platforms with microenvironment-responsive release and safety switches, establishing functional evaluation or release criteria for tumor therapy, and advancing cell-free approaches such as MSC-derived extracellular vesicles may enhance reproducibility and reduce risks associated with long-term persistence in vivo.
2026, 33(6):602-610.
DOI: 10.3872/j.issn.1007-385X.2026.06.002
Abstract:
[Abstract] Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable efficacy in hematologic malignancies, but conventional ex vivo manufacturing is limited by procedural complexity, long production cycles, and high cost. In vivo CAR-T cell generation directly reprograms T cells in patients through gene-delivery vectors and may simplify manufacturing and improve accessibility. Lentiviral vectors offer relatively large payload capacity, stable genomic integration, and mature manufacturing systems; however, broad tropism of native or pseudotyped envelopes may cause off-target transduction and safety risks. This review summarizes envelope pseudotyping and receptor- detargeting strategies based on the envelopes of vesicular stomatitis virus glycoprotein (VSV-G), Cocal virus glycoprotein (COCV-G), Sindbis virus, measles virus, and Nipah virus; discusses the selection of CD3, TCR, CD4, CD8, and CD7 as targeting receptors and the integration of CD2/CD28 costimulatory signals; and reviews preclinical studies and early clinical translation. Available evidence indicates that targeted lentiviral vectors can generate functional antitumor CAR-T cells in vivo, although insertional mutagenesis, off-target transduction, immunogenicity, dose control, and scalable manufacturing remain major challenges. This review provides a technical reference for the design and translation of next-generation in vivo CAR-T cell delivery systems.
[Abstract] Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable efficacy in hematologic malignancies, but conventional ex vivo manufacturing is limited by procedural complexity, long production cycles, and high cost. In vivo CAR-T cell generation directly reprograms T cells in patients through gene-delivery vectors and may simplify manufacturing and improve accessibility. Lentiviral vectors offer relatively large payload capacity, stable genomic integration, and mature manufacturing systems; however, broad tropism of native or pseudotyped envelopes may cause off-target transduction and safety risks. This review summarizes envelope pseudotyping and receptor- detargeting strategies based on the envelopes of vesicular stomatitis virus glycoprotein (VSV-G), Cocal virus glycoprotein (COCV-G), Sindbis virus, measles virus, and Nipah virus; discusses the selection of CD3, TCR, CD4, CD8, and CD7 as targeting receptors and the integration of CD2/CD28 costimulatory signals; and reviews preclinical studies and early clinical translation. Available evidence indicates that targeted lentiviral vectors can generate functional antitumor CAR-T cells in vivo, although insertional mutagenesis, off-target transduction, immunogenicity, dose control, and scalable manufacturing remain major challenges. This review provides a technical reference for the design and translation of next-generation in vivo CAR-T cell delivery systems.
2026, 33(6):611-618.
DOI: 10.3872/j.issn.1007-385X.2026.06.003
Abstract:
[Abstract] Objective: To develop CAR-T cells targeting fibroblast activation protein (FAP) expressed by cancer-associated fibroblasts (CAFs) and evaluate their ability to inhibit breast cancer growth by remodeling the tumor microenvironment (TME), providing a new candidate strategy for breast cancer CAR-T cell therapy. Methods: Nanobodies VHH1 and VHH2, which recognize distinct antigenic epitopes of FAP, were linked in tandem to generate a bivalent FAP antibody and to construct two CARs with different extracellular domain arrangements: FAP-CAR1 (VHH1-Linker-VHH2) and FAP-CAR2 (VHH2-Linker-VHH1). The resulting CAR constructs, containing the bivalent FAP antibody as the extracellular antigen-recognition domain, were individually cloned into retroviral vectors and packaged into viral particles. Murine lymphocytes were isolated and activated with anti-CD3/CD28 antibodies, followed by transduction to generate FAP-CAR1-T and FAP-CAR2-T cells. Targeted cytotoxicity of FAP-CAR-T cells was evaluated using real- time label-free dynamic cell analysis (RTCA) and flow cytometry (FCM), and IL-2 secretion was measured by ELISA. In a mouse 4T1- HER2 subcutaneous tumor model, the inhibitory effects of FAP-CAR-T, HER2-CAR-T, and untransduced T cells (Mock-T) on tumor · · 611 [[PAGE_INDEX=24 FILE=202606最新正文_1-30.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) growth were compared. Immunohistochemistry (IHC) was used to assess T cell infiltration in tumor tissues, and RNA sequencing was performed to analyze differentially expressed genes. Results: FAP-CAR1-T and FAP-CAR2-T cells expanded stably in vitro, with CAR positivity exceeding 60%. Both CAR-T cells specifically and efficiently killed NIH3T3 cells overexpressing mouse FAP (NIH3T3- mFAP), with FAP-CAR1-T showing superior expansion and IL-2 secretion compared to FAP-CAR2-T. Based on these results, FAP- CAR1-T was selected for subsequent in vivo experiments. In the 4T1-HER2 subcutaneous tumor model, FAP-CAR-T treatment significantly slowed tumor growth compared to the Mock-T group (P < 0.05), with no significant difference compared to the HER2- CAR-T group (P > 0.05). Compared to the Mock-T group, FAP-CAR-T treatment increased CD3 + T cell infiltration and reduced collagen deposition areas in tumor tissues. Transcriptomic analysis revealed that differentially expressed genes in the FAP-CAR-T group, compared to the Mock-T group (|log2FC| ≥1, P < 0.05), were primarily enriched in pathways related to extracellular matrix remodeling, immune response, and ECM-receptor interaction. Conclusion: FAP-CAR-T cells specifically target FAP-expressing stromal cells, remodel the tumor microenvironment, and significantly inhibit breast cancer growth. In terms of tumor volume control, FAP-CAR-T cells did not differ significantly from HER2-CAR-T cells, suggesting their potential as a candidate CAR-T approach for breast cancer.
[Abstract] Objective: To develop CAR-T cells targeting fibroblast activation protein (FAP) expressed by cancer-associated fibroblasts (CAFs) and evaluate their ability to inhibit breast cancer growth by remodeling the tumor microenvironment (TME), providing a new candidate strategy for breast cancer CAR-T cell therapy. Methods: Nanobodies VHH1 and VHH2, which recognize distinct antigenic epitopes of FAP, were linked in tandem to generate a bivalent FAP antibody and to construct two CARs with different extracellular domain arrangements: FAP-CAR1 (VHH1-Linker-VHH2) and FAP-CAR2 (VHH2-Linker-VHH1). The resulting CAR constructs, containing the bivalent FAP antibody as the extracellular antigen-recognition domain, were individually cloned into retroviral vectors and packaged into viral particles. Murine lymphocytes were isolated and activated with anti-CD3/CD28 antibodies, followed by transduction to generate FAP-CAR1-T and FAP-CAR2-T cells. Targeted cytotoxicity of FAP-CAR-T cells was evaluated using real- time label-free dynamic cell analysis (RTCA) and flow cytometry (FCM), and IL-2 secretion was measured by ELISA. In a mouse 4T1- HER2 subcutaneous tumor model, the inhibitory effects of FAP-CAR-T, HER2-CAR-T, and untransduced T cells (Mock-T) on tumor · · 611 [[PAGE_INDEX=24 FILE=202606最新正文_1-30.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) growth were compared. Immunohistochemistry (IHC) was used to assess T cell infiltration in tumor tissues, and RNA sequencing was performed to analyze differentially expressed genes. Results: FAP-CAR1-T and FAP-CAR2-T cells expanded stably in vitro, with CAR positivity exceeding 60%. Both CAR-T cells specifically and efficiently killed NIH3T3 cells overexpressing mouse FAP (NIH3T3- mFAP), with FAP-CAR1-T showing superior expansion and IL-2 secretion compared to FAP-CAR2-T. Based on these results, FAP- CAR1-T was selected for subsequent in vivo experiments. In the 4T1-HER2 subcutaneous tumor model, FAP-CAR-T treatment significantly slowed tumor growth compared to the Mock-T group (P < 0.05), with no significant difference compared to the HER2- CAR-T group (P > 0.05). Compared to the Mock-T group, FAP-CAR-T treatment increased CD3 + T cell infiltration and reduced collagen deposition areas in tumor tissues. Transcriptomic analysis revealed that differentially expressed genes in the FAP-CAR-T group, compared to the Mock-T group (|log2FC| ≥1, P < 0.05), were primarily enriched in pathways related to extracellular matrix remodeling, immune response, and ECM-receptor interaction. Conclusion: FAP-CAR-T cells specifically target FAP-expressing stromal cells, remodel the tumor microenvironment, and significantly inhibit breast cancer growth. In terms of tumor volume control, FAP-CAR-T cells did not differ significantly from HER2-CAR-T cells, suggesting their potential as a candidate CAR-T approach for breast cancer.
HUANG Zhiang
,
WANG Huiling
,
WU Mengyao
,
GUO Yipu
,
CHEN Yanming
,
ZHANG Liming
,
HUANG Le
,
ZHAO Qianwen
,
CHEN Jingying
2026, 33(6):619-629.
DOI: 10.3872/j.issn.1007-385X.2026.06.004
Abstract:
[Abstract] Objective: To investigate the role of bromodomain-containing protein 1 (BRD1) in the progression of non-small cell lung cancer (NSCLC) and its underlying mechanism through regulation of the PI3K/AKT signaling pathway. Methods: The predictive value of BRD1 as an immunotherapeutic biomarker was assessed using the TIMER 3.0 database. Human NSCLC cell lines A549 and NCI-H1299 stably overexpressing BRD1 or the N-terminal truncated mutant BRD1- ΔN were established using a lentiviral system. CCK-8, colony formation, wound healing, and Transwell assays were used to assess the effects of BRD1/BRD1-ΔN overexpression on cell proliferation and migration. Flow cytometry and Western blotting were used to detect cell apoptosis and the expression of apoptosis- related proteins. RNA-seq was employed to screen the signaling pathways affected by BRD1/BRD1- ΔN overexpression. Western blotting and in vitro kinase assays were used to detect the activation of AKT signaling pathways by overexpressing BRD1/BRD1-ΔN. To determine whether BRD1/BRD1-ΔN promotes cell proliferation and migration in an AKT-dependent manner, the AKT inhibitor · · 619 [[PAGE_INDEX=2 FILE=08b612ef-59ff-47e1-960e-f599d97bfff7.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) LY294002 was applied to NCI-H1299 cells overexpressing BRD1/BRD1- ΔN, followed by functional assays (CCK-8 and wound healing). RNA-seq combined with KEGG/GSEA analysis, co-immunoprecipitation (Co-IP), and RT-qPCR were performed to identify and validate integrin alpha-2 (ITGA2) as a key mediator that facilitates AKT activation. Co-IP, lentivirus-mediated ITGA2 knockdown, Western blotting, and functional experiments were then used to clarify the specific role of ITGA2 in BRD1-mediated AKT activation. Results: Database analysis showed that BRD1 could serve as a moderate predictive biomarker for immunotherapy in NSCLC (AUC = 0.625). Overexpression of BRD1/BRD1- ΔN significantly enhanced the proliferation and migration of NSCLC cells (all P < 0.01) without affecting apoptosis or the expression of apoptosis-related proteins (all P > 0.05). RNA-seq analysis indicated that BRD1/BRD1- ΔN overexpression primarily resulted in enrichment of the PI3K/AKT signaling pathway. Western blotting and in vitro kinase assays demonstrated that BRD1/BRD1-ΔN overexpression did not affect the phosphorylation of PDK1, an upstream kinase of AKT, nor alter the acetylation level of AKT (all P > 0.05). Treatment with the AKT inhibitor LY294002 revealed that BRD1/BRD1-ΔN promoted cell proliferation and migration partially through AKT activation. RT-qPCR and Western blotting confirmed that BRD1 overexpression upregulated ITGA2 at both mRNA and protein levels. Silencing ITGA2 reversed BRD1-induced AKT activation and the enhanced cell proliferation and migration. Conclusion: BRD1 is a novel oncogenic driver in NSCLC. It activates the AKT signaling pathway by upregulating ITGA2, thereby promoting the proliferation and migration of lung cancer cells.
[Abstract] Objective: To investigate the role of bromodomain-containing protein 1 (BRD1) in the progression of non-small cell lung cancer (NSCLC) and its underlying mechanism through regulation of the PI3K/AKT signaling pathway. Methods: The predictive value of BRD1 as an immunotherapeutic biomarker was assessed using the TIMER 3.0 database. Human NSCLC cell lines A549 and NCI-H1299 stably overexpressing BRD1 or the N-terminal truncated mutant BRD1- ΔN were established using a lentiviral system. CCK-8, colony formation, wound healing, and Transwell assays were used to assess the effects of BRD1/BRD1-ΔN overexpression on cell proliferation and migration. Flow cytometry and Western blotting were used to detect cell apoptosis and the expression of apoptosis- related proteins. RNA-seq was employed to screen the signaling pathways affected by BRD1/BRD1- ΔN overexpression. Western blotting and in vitro kinase assays were used to detect the activation of AKT signaling pathways by overexpressing BRD1/BRD1-ΔN. To determine whether BRD1/BRD1-ΔN promotes cell proliferation and migration in an AKT-dependent manner, the AKT inhibitor · · 619 [[PAGE_INDEX=2 FILE=08b612ef-59ff-47e1-960e-f599d97bfff7.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) LY294002 was applied to NCI-H1299 cells overexpressing BRD1/BRD1- ΔN, followed by functional assays (CCK-8 and wound healing). RNA-seq combined with KEGG/GSEA analysis, co-immunoprecipitation (Co-IP), and RT-qPCR were performed to identify and validate integrin alpha-2 (ITGA2) as a key mediator that facilitates AKT activation. Co-IP, lentivirus-mediated ITGA2 knockdown, Western blotting, and functional experiments were then used to clarify the specific role of ITGA2 in BRD1-mediated AKT activation. Results: Database analysis showed that BRD1 could serve as a moderate predictive biomarker for immunotherapy in NSCLC (AUC = 0.625). Overexpression of BRD1/BRD1- ΔN significantly enhanced the proliferation and migration of NSCLC cells (all P < 0.01) without affecting apoptosis or the expression of apoptosis-related proteins (all P > 0.05). RNA-seq analysis indicated that BRD1/BRD1- ΔN overexpression primarily resulted in enrichment of the PI3K/AKT signaling pathway. Western blotting and in vitro kinase assays demonstrated that BRD1/BRD1-ΔN overexpression did not affect the phosphorylation of PDK1, an upstream kinase of AKT, nor alter the acetylation level of AKT (all P > 0.05). Treatment with the AKT inhibitor LY294002 revealed that BRD1/BRD1-ΔN promoted cell proliferation and migration partially through AKT activation. RT-qPCR and Western blotting confirmed that BRD1 overexpression upregulated ITGA2 at both mRNA and protein levels. Silencing ITGA2 reversed BRD1-induced AKT activation and the enhanced cell proliferation and migration. Conclusion: BRD1 is a novel oncogenic driver in NSCLC. It activates the AKT signaling pathway by upregulating ITGA2, thereby promoting the proliferation and migration of lung cancer cells.
ZHAO Chuangchuang
,
QIN Qin
,
ZHU Haitao
,
ZHANG Zhengyang
,
LIU Yanfang
,
LIAO Xiang
,
Hsiang-i Tsai
2026, 33(6):630-640.
DOI: 10.3872/j.issn.1007-385X.2026.06.005
Abstract:
[Abstract] Objective: To investigate the role of galectin-9 (Gal-9) in promoting invasion and migration of pancreatic cancer cells and to elucidate the underlying mechanisms. Methods: Publicly available single-cell RNA sequencing datasets were analyzed to characterize the expression landscape of immune checkpoint molecules in pancreatic cancer. Western blotting and ELISA were performed to validate the expression and secretion profiles of galectin-9 (Gal-9) in pancreatic cancer cell lines and clinically relevant models. An orthotopic pancreatic tumor model was established in C57BL/6 mice. Immunohistochemistry, immunofluorescence staining, and flow cytometry were employed to evaluate the effects of Gal-9 on tumor cell proliferation, as well as on the infiltration and functional status of intratumoral CD8? T cells. Cancer-associated fibroblast (CAF) were treated with recombinant Gal-9 protein or tumor cell-derived conditioned medium (CM). Changes in type Ⅰ collagen expression in CAF were assessed by Western blotting, RT- qPCR, and immunofluorescence staining. Co-immunoprecipitation, immunofluorescence staining, and Western blotting were conducted to investigate the interaction between Gal-9 and CD44, as well as the activation of the JAK2/STAT3 signaling pathway. A subcutaneous · · 630 [[PAGE_INDEX=13 FILE=08b612ef-59ff-47e1-960e-f599d97bfff7.pdf]] 赵闯闯, 等. 半乳糖凝集素-9介导肿瘤相关成纤维细胞Ⅰ型胶原生成促进胰腺癌细胞侵袭与迁移xenograft model was established in nude mice by co-implanting Gal-9-overexpressing pancreatic cancer cells with CAF. Sirius Red staining and Masson's trichrome staining were performed to evaluate collagen deposition in tumor tissues. Extracellular matrix (ECM) proteins deposited by CAF were isolated using a decellularization approach. Wound healing assays, Transwell migration assays, and invasion assays were conducted to assess the effects of CAF-derived type Ⅰ collagen on the migratory and invasive capacities of pancreatic cancer cells. Functional rescue experiments were performed using siRNA-mediated knockdown of Gal-9. Results: Compared with classical immune checkpoint molecules PD-L1 and CTLA-4, Galectin-9 (Gal-9) was significantly upregulated in pancreatic cancer (P < 0.05). In vivo experiments demonstrated that Gal-9 promoted tumor growth (P < 0.01), accompanied by increased Ki-67 expression. Meanwhile, Gal-9 markedly reduced intratumoral CD8? T-cell infiltration and increased the proportion of TIM-3? cells, while the expression levels of Granzyme B, IFN-γ, and TNF-α were significantly decreased (P < 0.05). In vitro studies revealed that both exogenous Gal-9 and tumor cell-derived conditioned medium (CM) significantly upregulated type Ⅰ collagen expression in CAF (P < 0.001). Mechanistically, CD44 was detected in the immunoprecipitated complexes using anti-Gal-9 antibodies in CAF, and the protein expression levels of JAK2/STAT3 were correspondingly increased, indicating activation of the JAK2/STAT3 signaling pathway. Functional assays showed that treatment of pancreatic cancer cells with CAF-derived type Ⅰ collagen significantly enhanced their migratory and invasive capacities. In contrast, knockdown of Gal-9 in tumor cells resulted in reduced levels of CAF- derived type Ⅰ collagen, accompanied by a marked decrease in tumor cell migration and invasion. Conclusion: Tumor-derived Gal-9 may exert dual pro-tumorigenic functions in pancreatic cancer. It promotes tumor progression by enhancing cancer cell proliferation and inducing CD8? T cell exhaustion. In parallel, Gal-9 binds to CD44 on CAF to activate the JAK2/STAT3 pathway, thereby stimulating type Ⅰ collagen production and secretion, which in turn facilitates pancreatic cancer cell invasion and migration.
[Abstract] Objective: To investigate the role of galectin-9 (Gal-9) in promoting invasion and migration of pancreatic cancer cells and to elucidate the underlying mechanisms. Methods: Publicly available single-cell RNA sequencing datasets were analyzed to characterize the expression landscape of immune checkpoint molecules in pancreatic cancer. Western blotting and ELISA were performed to validate the expression and secretion profiles of galectin-9 (Gal-9) in pancreatic cancer cell lines and clinically relevant models. An orthotopic pancreatic tumor model was established in C57BL/6 mice. Immunohistochemistry, immunofluorescence staining, and flow cytometry were employed to evaluate the effects of Gal-9 on tumor cell proliferation, as well as on the infiltration and functional status of intratumoral CD8? T cells. Cancer-associated fibroblast (CAF) were treated with recombinant Gal-9 protein or tumor cell-derived conditioned medium (CM). Changes in type Ⅰ collagen expression in CAF were assessed by Western blotting, RT- qPCR, and immunofluorescence staining. Co-immunoprecipitation, immunofluorescence staining, and Western blotting were conducted to investigate the interaction between Gal-9 and CD44, as well as the activation of the JAK2/STAT3 signaling pathway. A subcutaneous · · 630 [[PAGE_INDEX=13 FILE=08b612ef-59ff-47e1-960e-f599d97bfff7.pdf]] 赵闯闯, 等. 半乳糖凝集素-9介导肿瘤相关成纤维细胞Ⅰ型胶原生成促进胰腺癌细胞侵袭与迁移xenograft model was established in nude mice by co-implanting Gal-9-overexpressing pancreatic cancer cells with CAF. Sirius Red staining and Masson's trichrome staining were performed to evaluate collagen deposition in tumor tissues. Extracellular matrix (ECM) proteins deposited by CAF were isolated using a decellularization approach. Wound healing assays, Transwell migration assays, and invasion assays were conducted to assess the effects of CAF-derived type Ⅰ collagen on the migratory and invasive capacities of pancreatic cancer cells. Functional rescue experiments were performed using siRNA-mediated knockdown of Gal-9. Results: Compared with classical immune checkpoint molecules PD-L1 and CTLA-4, Galectin-9 (Gal-9) was significantly upregulated in pancreatic cancer (P < 0.05). In vivo experiments demonstrated that Gal-9 promoted tumor growth (P < 0.01), accompanied by increased Ki-67 expression. Meanwhile, Gal-9 markedly reduced intratumoral CD8? T-cell infiltration and increased the proportion of TIM-3? cells, while the expression levels of Granzyme B, IFN-γ, and TNF-α were significantly decreased (P < 0.05). In vitro studies revealed that both exogenous Gal-9 and tumor cell-derived conditioned medium (CM) significantly upregulated type Ⅰ collagen expression in CAF (P < 0.001). Mechanistically, CD44 was detected in the immunoprecipitated complexes using anti-Gal-9 antibodies in CAF, and the protein expression levels of JAK2/STAT3 were correspondingly increased, indicating activation of the JAK2/STAT3 signaling pathway. Functional assays showed that treatment of pancreatic cancer cells with CAF-derived type Ⅰ collagen significantly enhanced their migratory and invasive capacities. In contrast, knockdown of Gal-9 in tumor cells resulted in reduced levels of CAF- derived type Ⅰ collagen, accompanied by a marked decrease in tumor cell migration and invasion. Conclusion: Tumor-derived Gal-9 may exert dual pro-tumorigenic functions in pancreatic cancer. It promotes tumor progression by enhancing cancer cell proliferation and inducing CD8? T cell exhaustion. In parallel, Gal-9 binds to CD44 on CAF to activate the JAK2/STAT3 pathway, thereby stimulating type Ⅰ collagen production and secretion, which in turn facilitates pancreatic cancer cell invasion and migration.
JIANG Lina
,
WANG Hao
,
WEI Hong
,
ZHAO Qian
,
HE Jun
,
CHI Qianwen
,
WEI Yilin
,
HE Yanran
,
FU Pengcheng
2026, 33(6):641-650.
DOI: 10.3872/j.issn.1007-385X.2026.06.006
Abstract:
[Abstract] Objective: To investigate the immunomodulatory mechanisms of the live attenuated measles, mumps and rubella vaccine (MMR) against triple-negative breast cancer (TNBC) via induction of immunogenic cell death (ICD). Methods: In vitro experiments: The CCK-8 assay was used to evaluate the effect of MMR on the viability of TNBC cell lines 4T1 and MDA-MB-231. Immunofluorescence was performed to detect the expression of calreticulin (CALR) in MDA-MB-231 cells. ATP was measured using a phosphomolybdic acid colorimetric assay, and high mobility group box 1 (HMGB1) levels in the cell supernatant were determined by ELISA. The GEPIA database was used to analyze the correlation between CALR/HMGB1 expression and the overall survival of breast · · 641 [[PAGE_INDEX=24 FILE=08b612ef-59ff-47e1-960e-f599d97bfff7.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) cancer patients. In vivo experiments: A TNBC mouse model was established by subcutaneous injection of 4T1-Luc cells into the mammary fat pad of female BALB/c mice. The mice were divided into three groups: Control group, doxorubicin hydrochloride (Dox) group, and MMR group. According to the grouping, intravenous administration was performed once every two days for a total of three consecutive doses. Tumor volume changes were monitored using an in vivo imaging system. Body weight and organ indices were recorded for preliminary safety assessment of vaccine. Histopathological changes in tumors were observed by hematoxylin-eosin (H-E) staining. The expression of CALR and HMGB1 in tumor tissues was detected by immunohistochemistry and Western blotting. Flow cytometry was used to analyze T lymphocyte subsets in the spleen, as well as the proportions of dendritic cells and macrophages in tumor. Immunohistochemistry was performed to detect CD8 + T lymphocyte infiltration in tumor tissues. The levels of pro-inflammatory cytokines IL-6 and TNF-α in serum were measured by ELISA. Results: MMR showed weak inhibitory effect on the viability of 4T1 cells but inhibited MDA-MB-231 cells by 90.39% (P < 0.001). Compared with the Control group, the MMR group exhibited upregulated expression of ICD-related proteins CALR, ATP and HMGB1 in MDA-MB-231 cells (P < 0.001). GEPIA database analysis indicated that patients with high expression of CALR and HMGB1 had prolonged survival. In vivo experiments, MMR delayed tumor volume growth (P < 0.001) and extended mouse survival. Within 28 days, there was no significant difference in body weight between the MMR group and the Control group (P > 0.05). H-E staining showed enlarged necrotic areas and immune cell infiltration in tumor tissues from the MMR group compared with the Control group. MMR upregulated the expression levels of the ICD-related proteins CALR and HMGB1. In the MMR group, the proportions of splenic CD4 + T and CD8 + T lymphocytes, as well as tumor-infiltrating dendritic cells and M1-type macrophages, were increased (P < 0.05). CD8 + T lymphocyte infiltration into tumors was also increased (P < 0.001), and the level of the pro-inflammatory cytokines IL-6 and TNF-α was upregulated (P < 0.01). Conclusion: The tumor- suppressive effect of the MMR vaccine on TNBC may be associated with the induction of ICD in tumors, thereby activating anti-tumor immunity.
[Abstract] Objective: To investigate the immunomodulatory mechanisms of the live attenuated measles, mumps and rubella vaccine (MMR) against triple-negative breast cancer (TNBC) via induction of immunogenic cell death (ICD). Methods: In vitro experiments: The CCK-8 assay was used to evaluate the effect of MMR on the viability of TNBC cell lines 4T1 and MDA-MB-231. Immunofluorescence was performed to detect the expression of calreticulin (CALR) in MDA-MB-231 cells. ATP was measured using a phosphomolybdic acid colorimetric assay, and high mobility group box 1 (HMGB1) levels in the cell supernatant were determined by ELISA. The GEPIA database was used to analyze the correlation between CALR/HMGB1 expression and the overall survival of breast · · 641 [[PAGE_INDEX=24 FILE=08b612ef-59ff-47e1-960e-f599d97bfff7.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) cancer patients. In vivo experiments: A TNBC mouse model was established by subcutaneous injection of 4T1-Luc cells into the mammary fat pad of female BALB/c mice. The mice were divided into three groups: Control group, doxorubicin hydrochloride (Dox) group, and MMR group. According to the grouping, intravenous administration was performed once every two days for a total of three consecutive doses. Tumor volume changes were monitored using an in vivo imaging system. Body weight and organ indices were recorded for preliminary safety assessment of vaccine. Histopathological changes in tumors were observed by hematoxylin-eosin (H-E) staining. The expression of CALR and HMGB1 in tumor tissues was detected by immunohistochemistry and Western blotting. Flow cytometry was used to analyze T lymphocyte subsets in the spleen, as well as the proportions of dendritic cells and macrophages in tumor. Immunohistochemistry was performed to detect CD8 + T lymphocyte infiltration in tumor tissues. The levels of pro-inflammatory cytokines IL-6 and TNF-α in serum were measured by ELISA. Results: MMR showed weak inhibitory effect on the viability of 4T1 cells but inhibited MDA-MB-231 cells by 90.39% (P < 0.001). Compared with the Control group, the MMR group exhibited upregulated expression of ICD-related proteins CALR, ATP and HMGB1 in MDA-MB-231 cells (P < 0.001). GEPIA database analysis indicated that patients with high expression of CALR and HMGB1 had prolonged survival. In vivo experiments, MMR delayed tumor volume growth (P < 0.001) and extended mouse survival. Within 28 days, there was no significant difference in body weight between the MMR group and the Control group (P > 0.05). H-E staining showed enlarged necrotic areas and immune cell infiltration in tumor tissues from the MMR group compared with the Control group. MMR upregulated the expression levels of the ICD-related proteins CALR and HMGB1. In the MMR group, the proportions of splenic CD4 + T and CD8 + T lymphocytes, as well as tumor-infiltrating dendritic cells and M1-type macrophages, were increased (P < 0.05). CD8 + T lymphocyte infiltration into tumors was also increased (P < 0.001), and the level of the pro-inflammatory cytokines IL-6 and TNF-α was upregulated (P < 0.01). Conclusion: The tumor- suppressive effect of the MMR vaccine on TNBC may be associated with the induction of ICD in tumors, thereby activating anti-tumor immunity.
2026, 33(6):651-660.
DOI: 10.3872/j.issn.1007-385X.2026.06.007
Abstract:
[Abstract] Objective: To elucidate the mechanism by which circular RNA (circRNA) regulates cisplatin (CDDP) resistance in tongue squamous cell carcinoma (TSCC). Methods: Chemosensitive and chemoresistant TSCC cells were used in this study. The differential expression of hsa_circ_0034762 in CAL27 and CAL27-res cells was detected by RT-qPCR. Cell apoptosis was evaluated by flow cytometry, and the autophagy-related protein p62, the LC3- Ⅱ/LC3- Ⅰ ratio were determined by Western blotting. The number of autophagosomes was observed by transmission electron microscopy (TEM). The targeting relationship between hsa_circ_0034762 and miR-17-3p was verified using a dual-luciferase reporter assay, and their co-localization in cells was detected by fluorescence in situ hybridization (FISH). Functional rescue experiments were performed by knocking down hsa_circ_0034762 alone or in combination with miR-17-3p inhibition. Results: Compared with parental chemosensitive cells, CAL27-res cells displayed significantly increased autophagy, as evidenced by an increased number of autophagosomes, an elevated LC3-Ⅱ/LC3-Ⅰ ratio, and decreased p62 protein expression. hsa_circ_0034762 was highly expressed in both chemoresistant TSCC tissues and CAL27-res cells. Knockdown of hsa_circ_0034762 significantly increased the apoptosis rate of CAL27-res cells, reduced the number of autophagosomes, upregulated p62 expression, and decreased the LC3-Ⅱ/LC3-Ⅰ ratio (all P < 0.05). Dual-luciferase reporter and FISH assays confirmed the targeted binding between hsa_circ_0034762 and miR-17-3p. Inhibition of miR-17-3p partially reversed the pro-apoptotic and autophagy- suppressive effects induced by hsa_circ_0034762 knockdown. Conclusion: hsa_circ_0034762 is overexpressed in chemoresistant TSCC tissues and cells. Knockdown of hsa_circ_0034762 suppresses autophagy and promotes apoptosis through miR-17-3p-mediated · · 651 [[PAGE_INDEX=2 FILE=7f0b8458-32b0-497d-b515-1deca828e6eb.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) regulation, thereby reducing the chemoresistance of TSCC cells.
[Abstract] Objective: To elucidate the mechanism by which circular RNA (circRNA) regulates cisplatin (CDDP) resistance in tongue squamous cell carcinoma (TSCC). Methods: Chemosensitive and chemoresistant TSCC cells were used in this study. The differential expression of hsa_circ_0034762 in CAL27 and CAL27-res cells was detected by RT-qPCR. Cell apoptosis was evaluated by flow cytometry, and the autophagy-related protein p62, the LC3- Ⅱ/LC3- Ⅰ ratio were determined by Western blotting. The number of autophagosomes was observed by transmission electron microscopy (TEM). The targeting relationship between hsa_circ_0034762 and miR-17-3p was verified using a dual-luciferase reporter assay, and their co-localization in cells was detected by fluorescence in situ hybridization (FISH). Functional rescue experiments were performed by knocking down hsa_circ_0034762 alone or in combination with miR-17-3p inhibition. Results: Compared with parental chemosensitive cells, CAL27-res cells displayed significantly increased autophagy, as evidenced by an increased number of autophagosomes, an elevated LC3-Ⅱ/LC3-Ⅰ ratio, and decreased p62 protein expression. hsa_circ_0034762 was highly expressed in both chemoresistant TSCC tissues and CAL27-res cells. Knockdown of hsa_circ_0034762 significantly increased the apoptosis rate of CAL27-res cells, reduced the number of autophagosomes, upregulated p62 expression, and decreased the LC3-Ⅱ/LC3-Ⅰ ratio (all P < 0.05). Dual-luciferase reporter and FISH assays confirmed the targeted binding between hsa_circ_0034762 and miR-17-3p. Inhibition of miR-17-3p partially reversed the pro-apoptotic and autophagy- suppressive effects induced by hsa_circ_0034762 knockdown. Conclusion: hsa_circ_0034762 is overexpressed in chemoresistant TSCC tissues and cells. Knockdown of hsa_circ_0034762 suppresses autophagy and promotes apoptosis through miR-17-3p-mediated · · 651 [[PAGE_INDEX=2 FILE=7f0b8458-32b0-497d-b515-1deca828e6eb.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) regulation, thereby reducing the chemoresistance of TSCC cells.
LI Guangwen
,
NIE Wenxun
,
GUO Jianhui
,
LIU Mengyuan
,
REN Qing
,
GUO Xiwen
,
CAI Shining
,
HE Zhenyan
,
YANG Wenli
2026, 33(6):661-669.
DOI: 10.3872/j.issn.1007-385X.2026.06.008
Abstract:
[Abstract] Objective: To evaluate the anti-tumor efficacy of FAP-CTLA-4 CAR-T cells targeting fibroblast activation protein (FAP) and secreting anti-CTLA-4 single-chain antibody (scFv) combined with apatinib in the treatment of glioblastoma (GBM), and to explore the underlying mechanisms. Methods: A FAP-CTLA-4 CAR overexpression vector was constructed and transduced into T cells to generate FAP-CTLA-4 CAR-T cells. In vitro functions of CAR-T cells were evaluated by flow cytometry (CD69 expression) and ELISPOT assay (IFN-γ secretion). Proliferation assays were used to assess the proliferation capacity of FAP-CTLA-4 CAR-T cells, and cytotoxicity assays were performed to evaluate the anti-tumor effect of the combination treatment with apatinib on U-87 MG cells. A mouse U-87 MG xenograft tumor model was established, and tumor-bearing mice were assigned to the monotherapy group (FAP- CTLA-4 CAR-T or apatinib alone) and the combination therapy group (FAP-CTLA-4 CAR-T plus apatinib). Tumor growth was monitored; tumor tissue Ki-67/CD31 expression was detected by immunohistochemistry and immunofluorescence; apoptosis was assessed by TUNEL staining. In vivo CAR-T persistence was analyzed by flow cytometry; treatment safety was assessed via H-E staining and serum biochemistry. Results: Compared with the monotherapy group, the combination therapy group showed significantly · · 661 [[PAGE_INDEX=12 FILE=7f0b8458-32b0-497d-b515-1deca828e6eb.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) increased CAR-T cell activation, enhanced proliferation capacity, a higher proportion of IFN-γ-secreting cells and superior cytotoxicity against target cells (P < 0.05 or P < 0.01).In the xenograft mouse model, the combination therapy markedly suppressed tumor growth and prolonged survival (P < 0.05 or P < 0.01), inhibited tumor cell proliferation and microvessel density, promoted tumor cell apoptosis, and extended the survival of CAR-T cells within tumor tissues (P < 0.05 or P < 0.01), without causing toxic damage to major organs. Conclusion: The combination of FAP-CTLA-4 CAR-T cells and apatinib exhibits synergistic anti-tumor effects in GBM, enhancing therapeutic efficacy while maintaining safety, and may represent a promising novel strategy for the treatment of this disease.
[Abstract] Objective: To evaluate the anti-tumor efficacy of FAP-CTLA-4 CAR-T cells targeting fibroblast activation protein (FAP) and secreting anti-CTLA-4 single-chain antibody (scFv) combined with apatinib in the treatment of glioblastoma (GBM), and to explore the underlying mechanisms. Methods: A FAP-CTLA-4 CAR overexpression vector was constructed and transduced into T cells to generate FAP-CTLA-4 CAR-T cells. In vitro functions of CAR-T cells were evaluated by flow cytometry (CD69 expression) and ELISPOT assay (IFN-γ secretion). Proliferation assays were used to assess the proliferation capacity of FAP-CTLA-4 CAR-T cells, and cytotoxicity assays were performed to evaluate the anti-tumor effect of the combination treatment with apatinib on U-87 MG cells. A mouse U-87 MG xenograft tumor model was established, and tumor-bearing mice were assigned to the monotherapy group (FAP- CTLA-4 CAR-T or apatinib alone) and the combination therapy group (FAP-CTLA-4 CAR-T plus apatinib). Tumor growth was monitored; tumor tissue Ki-67/CD31 expression was detected by immunohistochemistry and immunofluorescence; apoptosis was assessed by TUNEL staining. In vivo CAR-T persistence was analyzed by flow cytometry; treatment safety was assessed via H-E staining and serum biochemistry. Results: Compared with the monotherapy group, the combination therapy group showed significantly · · 661 [[PAGE_INDEX=12 FILE=7f0b8458-32b0-497d-b515-1deca828e6eb.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) increased CAR-T cell activation, enhanced proliferation capacity, a higher proportion of IFN-γ-secreting cells and superior cytotoxicity against target cells (P < 0.05 or P < 0.01).In the xenograft mouse model, the combination therapy markedly suppressed tumor growth and prolonged survival (P < 0.05 or P < 0.01), inhibited tumor cell proliferation and microvessel density, promoted tumor cell apoptosis, and extended the survival of CAR-T cells within tumor tissues (P < 0.05 or P < 0.01), without causing toxic damage to major organs. Conclusion: The combination of FAP-CTLA-4 CAR-T cells and apatinib exhibits synergistic anti-tumor effects in GBM, enhancing therapeutic efficacy while maintaining safety, and may represent a promising novel strategy for the treatment of this disease.
2026, 33(6):670-677.
DOI: 10.3872/j.issn.1007-385X.2026.06.009
Abstract:
[Abstract] Objective: To investigate the effect of oenothein B on the malignant biological behavior of ovarian cancer SKOV3 cells by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor-kappa B (NF-κB) pathway. Methods: The half-maximal inhibitory concentration (IC50) of oenothein B on SKOV3 cells was determined by the CCK-8 assay, and the subsequent experimental doses were determined based on the IC50 value and relevant literature. SKOV3 cells were divided into the control group, low-dose oenothein B group (6.25 μmol/L), medium-dose oenothein B group (12.5 μmol/L), high-dose oenothein B group (25 μmol/L), PI3K inhibitor (LY294002) group, and high-dose oenothein B combined with PI3K activator (740Y-P) group. The cell proliferation ability of each group was detected by CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) staining. Transwell invasion assay, wound healing assay and flow cytometry were used to detect cell invasion, migration ability and apoptosis in each group, respectively. RT- qPCR was applied to detect the mRNA expression levels of proliferation-related gene Cyclin D1, migration-related gene migration and invasion enhancer 1 (MIEN1), and apoptosis-related gene p53 in each group. Western blotting was used to determine the expression levels of PI3K/AKT/NF-κB pathway-related proteins including p-PI3K, p-AKT and NF-κB p65 in each group. Results: The IC50 value · · 670 [[PAGE_INDEX=2 FILE=37dae296-6188-4ec2-9b39-45b08e05f9a4.pdf]] 张颖, 等. 月见草素B调控PI3K/AKT/NF-κB通路对卵巢癌SKOV3细胞恶性生物学行为的影响of oenothein B against SKOV3 cells after 24 h of treatment was 28.70 μmol/L. Compared with the control group, the proliferation ability, number of invasive cells and wound healing rate of SKOV3 cells were significantly decreased in the low-, medium- and high- dose oenothein B groups as well as the LY294002 group (all P < 0.05); the mRNA expression levels of Cyclin D1 and MIEN1, as well as the protein expression levels of p-PI3K, p-AKT and NF-κB p65 were markedly downregulated (all P < 0.05), while the cell apoptosis rate and p53 mRNA expression were remarkably upregulated (all P < 0.05). Compared with the LY294002 group, the high-dose oenothein B exhibited more pronounced inhibitory effects on cell proliferation, invasion, and migration (all P < 0.05), as well as greater downregulation of Cyclin D1 and MIEN1 mRNA and p-PI3K, p-AKT, and NF- κB p65 protein expression, and more significant upregulation of apoptosis rate and p53 mRNA expression (all P < 0.05). Compared with the high-dose oenothein B group, the high-dose oenothein B + 740Y-P group showed increased cell proliferation, invasion, and migration (all P < 0.05), upregulated Cyclin D1 and MIEN1 mRNA and p-PI3K, p-AKT, and NF-κB p65 protein expression (all P < 0.05), and decreased apoptosis rate and p53 mRNA expression (all P < 0.05). Conclusion: Oenothein B may inhibit the PI3K/AKT/NF- κB signaling pathway, thereby suppressing the proliferation, invasion and migration of ovarian cancer SKOV3 cells and inducing cell apoptosis.
[Abstract] Objective: To investigate the effect of oenothein B on the malignant biological behavior of ovarian cancer SKOV3 cells by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor-kappa B (NF-κB) pathway. Methods: The half-maximal inhibitory concentration (IC50) of oenothein B on SKOV3 cells was determined by the CCK-8 assay, and the subsequent experimental doses were determined based on the IC50 value and relevant literature. SKOV3 cells were divided into the control group, low-dose oenothein B group (6.25 μmol/L), medium-dose oenothein B group (12.5 μmol/L), high-dose oenothein B group (25 μmol/L), PI3K inhibitor (LY294002) group, and high-dose oenothein B combined with PI3K activator (740Y-P) group. The cell proliferation ability of each group was detected by CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) staining. Transwell invasion assay, wound healing assay and flow cytometry were used to detect cell invasion, migration ability and apoptosis in each group, respectively. RT- qPCR was applied to detect the mRNA expression levels of proliferation-related gene Cyclin D1, migration-related gene migration and invasion enhancer 1 (MIEN1), and apoptosis-related gene p53 in each group. Western blotting was used to determine the expression levels of PI3K/AKT/NF-κB pathway-related proteins including p-PI3K, p-AKT and NF-κB p65 in each group. Results: The IC50 value · · 670 [[PAGE_INDEX=2 FILE=37dae296-6188-4ec2-9b39-45b08e05f9a4.pdf]] 张颖, 等. 月见草素B调控PI3K/AKT/NF-κB通路对卵巢癌SKOV3细胞恶性生物学行为的影响of oenothein B against SKOV3 cells after 24 h of treatment was 28.70 μmol/L. Compared with the control group, the proliferation ability, number of invasive cells and wound healing rate of SKOV3 cells were significantly decreased in the low-, medium- and high- dose oenothein B groups as well as the LY294002 group (all P < 0.05); the mRNA expression levels of Cyclin D1 and MIEN1, as well as the protein expression levels of p-PI3K, p-AKT and NF-κB p65 were markedly downregulated (all P < 0.05), while the cell apoptosis rate and p53 mRNA expression were remarkably upregulated (all P < 0.05). Compared with the LY294002 group, the high-dose oenothein B exhibited more pronounced inhibitory effects on cell proliferation, invasion, and migration (all P < 0.05), as well as greater downregulation of Cyclin D1 and MIEN1 mRNA and p-PI3K, p-AKT, and NF- κB p65 protein expression, and more significant upregulation of apoptosis rate and p53 mRNA expression (all P < 0.05). Compared with the high-dose oenothein B group, the high-dose oenothein B + 740Y-P group showed increased cell proliferation, invasion, and migration (all P < 0.05), upregulated Cyclin D1 and MIEN1 mRNA and p-PI3K, p-AKT, and NF-κB p65 protein expression (all P < 0.05), and decreased apoptosis rate and p53 mRNA expression (all P < 0.05). Conclusion: Oenothein B may inhibit the PI3K/AKT/NF- κB signaling pathway, thereby suppressing the proliferation, invasion and migration of ovarian cancer SKOV3 cells and inducing cell apoptosis.
2026, 33(6):678-689.
DOI: 10.3872/j.issn.1007-385X.2026.06.010
Abstract:
[Abstract] Objective: To investigate the role of m6A regulators in prognostic evaluation, immune microenvironment characteristics, and treatment response in cervical cancer, to construct a prognostic risk model based on m6A regulators, and to analyze its associations with immune infiltration, drug sensitivity, and intercellular communication. Methods: Transcriptomic data of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) from the TCGA and GEO databases were used to analyze the expression and mutation profiles of 22 m6A regulators. A prognostic risk model was established using LASSO?Cox regression, and patients were stratified into high? and low?risk groups based on risk scores. Immune cell infiltration and microenvironment characteristics were evaluated using CIBERSORT and ESTIMATE algorithms. Antitumor drug sensitivity was predicted using oncoPredict. Single?cell transcriptomic data (E?MTAB?12305) were integrated to analyze intercellular communication networks using CellChat. Results: A total of 12 differentially expressed m6A regulators were identified in cervical cancer. Patients in the high?risk group showed significantly shorter overall survival (P < 0.05), lower immune scores, and reduced sensitivity to antitumor drugs such as paclitaxel, fluorouracil, and doxorubicin, as indicated by higher IC50 values. Single?cell analysis revealed altered intercellular communication networks in cervical cancer tissues, with interactions between T cells and endothelial/epithelial cells mainly mediated by the CCL5?ACKR1 and MIF?(CD74 + CXCR4) ligand?receptor pairs. Validation of key m6A regulators at the mRNA and protein levels in clinical samples showed that most regulators were significantly more highly expressed in cervical cancer tissues than in healthy human cervical tissues. Conclusion: The m6A regulator-based prognostic signature can effectively predict the prognosis of patients with cervical cancer. The risk score is closely associated with tumor immune infiltration, drug sensitivity, and intercellular communication, providing a novel molecular basis for · · 678 [[PAGE_INDEX=10 FILE=37dae296-6188-4ec2-9b39-45b08e05f9a4.pdf]] 蒋本贵, 等. 基于m6A调控因子的预后模型与宫颈癌免疫浸润、药物敏感性及细胞间通信的综合分析prognostic stratification and personalized therapy in cervical cancer.
[Abstract] Objective: To investigate the role of m6A regulators in prognostic evaluation, immune microenvironment characteristics, and treatment response in cervical cancer, to construct a prognostic risk model based on m6A regulators, and to analyze its associations with immune infiltration, drug sensitivity, and intercellular communication. Methods: Transcriptomic data of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) from the TCGA and GEO databases were used to analyze the expression and mutation profiles of 22 m6A regulators. A prognostic risk model was established using LASSO?Cox regression, and patients were stratified into high? and low?risk groups based on risk scores. Immune cell infiltration and microenvironment characteristics were evaluated using CIBERSORT and ESTIMATE algorithms. Antitumor drug sensitivity was predicted using oncoPredict. Single?cell transcriptomic data (E?MTAB?12305) were integrated to analyze intercellular communication networks using CellChat. Results: A total of 12 differentially expressed m6A regulators were identified in cervical cancer. Patients in the high?risk group showed significantly shorter overall survival (P < 0.05), lower immune scores, and reduced sensitivity to antitumor drugs such as paclitaxel, fluorouracil, and doxorubicin, as indicated by higher IC50 values. Single?cell analysis revealed altered intercellular communication networks in cervical cancer tissues, with interactions between T cells and endothelial/epithelial cells mainly mediated by the CCL5?ACKR1 and MIF?(CD74 + CXCR4) ligand?receptor pairs. Validation of key m6A regulators at the mRNA and protein levels in clinical samples showed that most regulators were significantly more highly expressed in cervical cancer tissues than in healthy human cervical tissues. Conclusion: The m6A regulator-based prognostic signature can effectively predict the prognosis of patients with cervical cancer. The risk score is closely associated with tumor immune infiltration, drug sensitivity, and intercellular communication, providing a novel molecular basis for · · 678 [[PAGE_INDEX=10 FILE=37dae296-6188-4ec2-9b39-45b08e05f9a4.pdf]] 蒋本贵, 等. 基于m6A调控因子的预后模型与宫颈癌免疫浸润、药物敏感性及细胞间通信的综合分析prognostic stratification and personalized therapy in cervical cancer.
2026, 33(6):690-697.
DOI: 10.3872/j.issn.1007-385X.2026.06.011
Abstract:
[摘 要] 胰岛素样生长因子2 mRNA结合蛋白1（IGF2BP1）作为关键的N6-甲基腺苷（m?A）修饰阅读器，不仅能通过稳定癌基因转录本直接驱动肿瘤进展，还能作为核心枢纽塑造肿瘤免疫抑制性微环境、促进免疫逃逸。本综述系统阐释了IGF2BP1通过稳定程序性死亡配体1（PD-L1）、C-C基序趋化因子配体2（CCL2）等免疫关键分子的mRNA，影响髓源性抑制细胞（MDSC）募集、 巨噬细胞极化和T细胞功能，从而介导免疫逃逸新机制。本文还深入梳理了以2-[(5-溴-2-噻吩基)亚甲氨基]苯甲酰胺（BTYNB）、 葫芦素B（CuB）及其衍生物为代表的小分子抑制剂的研究进展，这些抑制剂通过靶向IGF2BP1的不同结构域阻断其功能。最后， 本综述展望了靶向IGF2BP1联合免疫检查点抑制剂等策略在逆转肿瘤免疫抑制方面的巨大潜力和面临的挑战。本文旨在为靶向IGF2BP1的肿瘤免疫治疗提供新的理论依据和研究方向。
[摘 要] 胰岛素样生长因子2 mRNA结合蛋白1（IGF2BP1）作为关键的N6-甲基腺苷（m?A）修饰阅读器，不仅能通过稳定癌基因转录本直接驱动肿瘤进展，还能作为核心枢纽塑造肿瘤免疫抑制性微环境、促进免疫逃逸。本综述系统阐释了IGF2BP1通过稳定程序性死亡配体1（PD-L1）、C-C基序趋化因子配体2（CCL2）等免疫关键分子的mRNA，影响髓源性抑制细胞（MDSC）募集、 巨噬细胞极化和T细胞功能，从而介导免疫逃逸新机制。本文还深入梳理了以2-[(5-溴-2-噻吩基)亚甲氨基]苯甲酰胺（BTYNB）、 葫芦素B（CuB）及其衍生物为代表的小分子抑制剂的研究进展，这些抑制剂通过靶向IGF2BP1的不同结构域阻断其功能。最后， 本综述展望了靶向IGF2BP1联合免疫检查点抑制剂等策略在逆转肿瘤免疫抑制方面的巨大潜力和面临的挑战。本文旨在为靶向IGF2BP1的肿瘤免疫治疗提供新的理论依据和研究方向。
12 Formation mechanisms and advances in biotherapy for malignant pleural effusion and malignant ascites
2026, 33(6):698-702.
DOI: 10.3872/j.issn.1007-385X.2026.06.012
Abstract:
[摘 要] 恶性胸腔积液和恶性腹水（MPE/MA）是晚期肿瘤患者常见并发症，预后极差，其形成涉及血管与淋巴管通透性异常、 肿瘤细胞体腔种植及肿瘤微环境（TME）失衡等多重复杂机制。近年来，随着对TME调控机制的深入探索，生物治疗已成为突破传统治疗瓶颈的关键策略。本文系统阐述MPE/MA形成的核心机制，重点总结了以靶向治疗、免疫治疗及新型药物递送系统为代表的生物治疗最新进展；并对当前面临的挑战及未来发展方向进行了深入探讨，以期为临床实践与转化研究提供理论依据与思路。
[摘 要] 恶性胸腔积液和恶性腹水（MPE/MA）是晚期肿瘤患者常见并发症，预后极差，其形成涉及血管与淋巴管通透性异常、 肿瘤细胞体腔种植及肿瘤微环境（TME）失衡等多重复杂机制。近年来，随着对TME调控机制的深入探索，生物治疗已成为突破传统治疗瓶颈的关键策略。本文系统阐述MPE/MA形成的核心机制，重点总结了以靶向治疗、免疫治疗及新型药物递送系统为代表的生物治疗最新进展；并对当前面临的挑战及未来发展方向进行了深入探讨，以期为临床实践与转化研究提供理论依据与思路。
2026, 33(6):703-708.
DOI: 10.3872/j.issn.1007-385X.2026.06.013
Abstract:
[摘 要] 嵌合抗原受体T细胞（CAR-T细胞）疗法在复发/难治性恶性血液肿瘤中已显示出较好疗效，但在实体瘤中的疗效仍受多重因素限制。本文在简述CAR-T细胞疗法在血液肿瘤与实体瘤中临床研究进展的基础上，重点梳理其在靶点选择与抗原异质性、肿瘤免疫抑制性微环境、T细胞归巢与浸润不足、体内持续性不足、制备工艺限制，以及不良反应与安全性、可控性等方面面临的关键挑战，并总结多靶点或逻辑门控CAR设计、装甲CAR-T细胞与联合治疗、局部递送与归巢增强、安全开关与剂量优化、同种异体通用型CAR-T细胞等应对策略，以期为CAR-T细胞治疗恶性肿瘤的进一步优化与临床转化提供参考。
[摘 要] 嵌合抗原受体T细胞（CAR-T细胞）疗法在复发/难治性恶性血液肿瘤中已显示出较好疗效，但在实体瘤中的疗效仍受多重因素限制。本文在简述CAR-T细胞疗法在血液肿瘤与实体瘤中临床研究进展的基础上，重点梳理其在靶点选择与抗原异质性、肿瘤免疫抑制性微环境、T细胞归巢与浸润不足、体内持续性不足、制备工艺限制，以及不良反应与安全性、可控性等方面面临的关键挑战，并总结多靶点或逻辑门控CAR设计、装甲CAR-T细胞与联合治疗、局部递送与归巢增强、安全开关与剂量优化、同种异体通用型CAR-T细胞等应对策略，以期为CAR-T细胞治疗恶性肿瘤的进一步优化与临床转化提供参考。
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- 刊号：ISSN 1007-385X
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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.