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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.
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.
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.
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Objective: To develop a chimeric costimulatory receptor targeting CD7 and prepare γδ T cells from healthy donors for the evaluation of its in vitro and in vivo cytotoxic effects against T-cell acute lymphoblastic leukemia (T-ALL) cells. Methods: γδ T cells expressing the CD7-targeting chimeric costimulatory receptor (CD7-DAP10-CCR-γδ T) were constructed. Using lentiviral transduction, the receptor was introduced into human peripheral blood-derived γδ T cells from healthy donors, followed by ex vivo expansion with artificial antigen-presenting cell (aAPC) expressing CD64, CD86, and CD137L. The cytotoxic activity of CD7-DAP10-CCR-γδ T cells against T-ALL cells (Jurkat), CD7-deficient Jurkat cells (CD7? Jurkat), and normal primary αβ T cells was assessed using the Annexin V/7-AAD assay. Furthermore, the in vivo efficacy was evaluated in an immunodeficient mouse model bearing T-ALL xenografts. Tumor burden was monitored regularly via in vivo imaging, and body weight changes and survival rates were recorded. Results: CD7-DAP10-CCR-γδ T cells were successfully expanded using aAPC, achieving an average expansion fold exceeding 10000. In vitro cytotoxicity assays demonstrated that these cells exhibited significantly high killing activity against T-ALL cells and Jurkat cells (P < 0.01), while showing limited cytotoxicity against CD7? Jurkat cells and negligible effects on normal primary CD7-high αβ T cells. In the T-ALL xenograft model, treatment with CD7-DAP10-CCR-γδ T cells resulted in a significant prolongation of survival compared to the PBS control group. Conclusion: This study establishes a robust aAPC-driven protocol for generating CD7-DAP10-CCR-γδ T cells with scalable expansion ( > 10 000-fold) and CD7-specific anti-tumor efficacy. The engineered cells exhibited selective cytotoxicity against T-ALL while sparing normal T cells, highlighting their therapeutic promise for relapsed/refractory T-ALL with mitigated on-target/off-tumor risks.
Objective: To develop a chimeric costimulatory receptor targeting CD7 and prepare γδ T cells from healthy donors for the evaluation of its in vitro and in vivo cytotoxic effects against T-cell acute lymphoblastic leukemia (T-ALL) cells. Methods: γδ T cells expressing the CD7-targeting chimeric costimulatory receptor (CD7-DAP10-CCR-γδ T) were constructed. Using lentiviral transduction, the receptor was introduced into human peripheral blood-derived γδ T cells from healthy donors, followed by ex vivo expansion with artificial antigen-presenting cell (aAPC) expressing CD64, CD86, and CD137L. The cytotoxic activity of CD7-DAP10-CCR-γδ T cells against T-ALL cells (Jurkat), CD7-deficient Jurkat cells (CD7? Jurkat), and normal primary αβ T cells was assessed using the Annexin V/7-AAD assay. Furthermore, the in vivo efficacy was evaluated in an immunodeficient mouse model bearing T-ALL xenografts. Tumor burden was monitored regularly via in vivo imaging, and body weight changes and survival rates were recorded. Results: CD7-DAP10-CCR-γδ T cells were successfully expanded using aAPC, achieving an average expansion fold exceeding 10000. In vitro cytotoxicity assays demonstrated that these cells exhibited significantly high killing activity against T-ALL cells and Jurkat cells (P < 0.01), while showing limited cytotoxicity against CD7? Jurkat cells and negligible effects on normal primary CD7-high αβ T cells. In the T-ALL xenograft model, treatment with CD7-DAP10-CCR-γδ T cells resulted in a significant prolongation of survival compared to the PBS control group. Conclusion: This study establishes a robust aAPC-driven protocol for generating CD7-DAP10-CCR-γδ T cells with scalable expansion ( > 10 000-fold) and CD7-specific anti-tumor efficacy. The engineered cells exhibited selective cytotoxicity against T-ALL while sparing normal T cells, highlighting their therapeutic promise for relapsed/refractory T-ALL with mitigated on-target/off-tumor risks.
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2012,19(5):550-555, DOI: 10.3872/j.issn.1007-385X.2012.5.018
Abstract:
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
2016,23(2):149-160, DOI: 10.3872/j.issn.1007-385X.2016.02.001
Abstract:
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
2018,25(1):23-27, DOI: 10.3872/j.issn.1007-385X.2018.01.004
Abstract:
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
2010,17(1):57-61, DOI: 10.3872/j.issn.1007-385X.2010.1.011
Abstract:
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
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Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.