Immunoediting instructs tumor metabolic reprogramming to support immune evasion [ExomeSeq]

Immunoediting sculpts immunogenicity and thwarts host anti-tumor responses in tumor cells during tumorigenesis; however, it remains unknown whether metabolic programming of tumor cells can be guided by immunosurveillance. Here, we report that T cell-mediated immunosurveillance in early staged tumorigenesis instructs c-Myc upregulation and metabolic reprogramming in tumor cells. This previously unexplored tumor-immune interaction is controlled by a non-canonical IFNg-STAT3 signaling and supports tumor immune evasion. Our findings uncover that immunoediting instructs deregulated bioenergetic programs in tumor cells for empowering them to disarm the T cell-mediated immunosurveillance by imposing metabolic tug-of-war between tumor and infiltrating T cells and forming the suppressive tumor microenvironment. Overall design: Examination of genetic mutation in tumor cell grown from immunocompetent and immunocompromised mice

免疫编辑（Immunoediting）在肿瘤发生过程中可塑造肿瘤细胞的免疫原性，并阻碍宿主的抗肿瘤免疫应答；然而目前仍不清楚，肿瘤细胞的代谢编程是否可受免疫监视（Immunosurveillance）调控。本研究报道，早期肿瘤发生阶段的T细胞介导的免疫监视，可诱导肿瘤细胞内c-Myc上调与代谢重编程（metabolic reprogramming）。这一此前尚未被探明的肿瘤-免疫互作过程受非经典IFNγ-STAT3信号通路调控，并可促进肿瘤免疫逃逸。我们的研究发现，免疫编辑可诱导肿瘤细胞出现失调的生物能量程序，使肿瘤细胞通过与浸润性T细胞展开代谢拉锯，从而削弱T细胞介导的免疫监视，并最终形成免疫抑制性肿瘤微环境。总体实验设计：对源自免疫健全小鼠与免疫缺陷小鼠的肿瘤细胞进行基因突变检测。