CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:OT-I TCR Transgenic Mice to Study the Role of PTPN22 in Anti-cancer Immunity.
OT-I TCR Transgenic Mice to Study the Role of PTPN22 in Anti-cancer Immunity.
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蛋白酪氨酸磷酸酶非受体22型(PTPN22)是免疫细胞活化和反应的关键调节因子。PTPN22的遗传多态性与自身免疫性疾病发病风险增加密切相关,而对PTPN22缺陷小鼠品系的分析已确定PTPN22是T细胞抗原受体信号传导的负调节因子。除了在维持免疫耐受中的这些关键作用外,PTPN22还作为T细胞抗肿瘤反应的细胞内检查点,提示PTPN22可能是改善T细胞免疫治疗的有用靶点。为评估靶向PTPN22的潜力,我们将Ptpn22缺陷小鼠与OT-I TCR转基因背景杂交,并在小鼠肿瘤模型中采用过继性T细胞转移方法。我们提供了用于体外扩增效应OT-I细胞毒性T淋巴细胞的 basic 方法、体外表型分析以及体内过继性T细胞转移模型,以评估PTPN22在抗肿瘤免疫中的作用。
Phosphotyrosine phosphatase non-receptor type 22 (PTPN22) is a key regulator of immune cell activation and responses. Genetic polymorphisms of PTPN22 have been strongly linked with an increased risk of developing autoimmune diseases, while analysis of PTPN22-deficient mouse strains has determined that PTPN22 serves as a negative regulator of T cell antigen receptor signaling.
As well as these key roles in maintaining immune tolerance, PTPN22 acts as an intracellular checkpoint for T cell responses to cancer, suggesting that PTPN22 might be a useful target to improve T cell immunotherapies. To assess the potential for targeting PTPN22, we have crossed Ptpn22-deficient mice to an OT-I TCR transgenic background and used adoptive T cell transfer approaches in mouse cancer models.
We provide basic methods for the in vitro expansion of effector OT-I cytotoxic T lymphocytes, in vitro phenotypic analysis, and in vivo adoptive T cell transfer models to assess the role of PTPN22 in anti-cancer immunity.
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