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2篇 您的检索式:作者名="Weiting Ge"
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1Pan-cancer analyses demonstrate that ANKRD6 is associated with a poor prognosis and correlates with M2 macrophage infiltration in colon cancer显示文摘Objective:Ankyrin repeat domain-containing protein 6(ANKRD6)is an ankyrin repeat-containing protein which is structurally related to vertebrate inversin and Drosophila Diego.However,the correlations between ANKRD6 and tumor-infiltrating immune cells in cancers is not clear.Methods:ANKRD6 expression was analyzed by Oncomine,Tumor Immune Estimation Resource(TIMER)and Gene Expression Profiling Interactive Analysis(GEPIA).PrognoScan and GEPIA were used to evaluate the influence of ANKRD6 on clinical prognosis.TIMER and CIBERSORT were used to analyze correlations between ANKRD6 expression levels and tumor immune cell infiltrates.Immunohistochemical analysis of the relationship between ANKRD6 expression and overall survival,as well as the relationship between ANKRD6 expression and M2 macrophage infiltration,was performed.Results:High level of ANKRD6 expression was associated with poor prognosis of colon cancer.ANKRD6 expression level was positively correlated with infiltrating levels of CD8+T cells,CD4+T cells,macrophages,neutrophils and dendritic cells in colon cancer by using TIMER.Using CIBERSORT,we found that in plasma cells,CD8+T cells,CD4+memory resting T cells,follicular helper T cells and activated natural killer cells were significantly lower in the ANKRD6-high group than in the ANKRD6-low group.M0 and M2 macrophages were significantly higher in the ANKRD6-high group than in the ANKRD6-low group.Immunohistochemistry confirmed that M2 macrophage infiltration in the ANKRD6-high group significantly increased.Conclusions:The high ANKRD6 expression is associated with poor prognosis of colon cancer.ANKRD6 expression is positively correlated with M2 macrophage infiltration in colon cancer.Rui Bai Dehao Wu Zhong Shi Wangxiong Hu Juan Li Yuanyuan Chen Weiting Ge Ying Yuan Shu Zheng 2021Chinese Journal of Cancer Research2021,33,1:1
2A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis显示文摘Pleural and peritoneal metastasis accompanied by malignant pleural effusion(MPE)or malignant ascites(MA)is frequent in patients with advanced solid tumors that originate from the lung,breast,gastrointestinal tract and ovary.Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination in serous cavities.However,malignant effusions constitute an immune-suppressive environment that potentially induces CAR-T cell dysfunction.Here,we demonstrated that the anti-tumor cytotoxicity of conventional 2nd-generation CAR-T cells was significantly inhibited by both the cellular and non-cellular components of MPE/MA,which was primarily attributed to impaired CAR-T cell proliferation and cytokine production in MPE/MA environment.Interestingly,we found that PD-L1 was widely expressed on freshly-isolated MPE/MA cells.Based on this feature,a novel PD-L1-targeting chimeric switch receptor(PD-L1.BB CSR)was designed,which can bind to PD-L1,switching the inhibitory signal into an additional 4-1BB signal.When co-expressed with a 2nd-generation CAR,PD-L1.BB CSR-modified CAR-T cells displayed superior fitness and enhanced functions in both culture medium and MPE/MA environment,causing rapid and durable eradication of pleural and peritoneal metastatic tumors in xenograft models.Further investigations revealed elevated expressions of T-cell activation,proliferation,and cytotoxicity-related genes,and we confirmed that PD-L1 scFv and 4-1BB intracellular domain,the two important components of PD-L1.BB CSR,were both necessary for the functional improvements of CAR-T cells.Overall,our study shed light on the clinical application of PD-L1.BB CSR-modified dual-targeting CAR-T cells.Based on this study,a phase I clinical trial was initiated in patients with pleural or peritoneal metastasis(NCT04684459).Qizhi Ma Xia He Benxia Zhang Fuchun Guo Xuejin Ou Qiyu Yang Pei Shu Yue Chen Kai Li Ge Gao Yajuan Zhu Diyuan Qin Jie Tang Xiaoyu Li Meng Jing Jian Zhao Zeming Mo Ning Liu Yao Zeng Kexun Zhou Mingyang Feng Weiting Liao Wanting Lei Qiu Li Dan Li Yongsheng Wang 2022Signal Transduction and Targeted Therapy2022,7,12:0
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