Immunoediting instructs tumor metabolic reprogramming to support immune evasion

Immunoediting sculpts immunogenicity and thwarts host anti-tumor responses in tumor cells during tumor-igenesis; 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-stage tumorigenesis instructs c-Myc upregulation and metabolic reprogramming in tumor cells. This previously unexplored tu-mor-immune interaction is controlled by non-canonical interferon gamma (IFNg)-STAT3 signaling and sup-ports tumor immune evasion. Our findings uncover that immunoediting instructs deregulated bioenergetic programs in tumor cells to empower 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 microenvi-ronment.

Automated summary

T cell-mediated immunosurveillance in early-stage tumorigenesis guides metabolic reprogramming in tumor cells through non-canonical interferon gamma (IFNg)-STAT3 signaling, leading to immune evasion and the formation of a suppressive tumor microenvironment.