Oncogenic signaling is known for directly driving cancer progression, but here Nguyen and Spranger review the role of oncogenic signaling in inhibiting antitumor immunity. Some tumor intrinsic pathways (including WNT-β-catenin signaling, prostaglandin E2 production, loss of p53 or PTEN, MYC upregulation, epigenetic markers) directly impair APC, NK cell, and T cell recruitment, and NK cell and T cell antitumor activity, while other pathways (including loss of function mutations in LKB1, and increased focal adhesion kinase activity) recruit and support regulatory immune cells including immunosuppressive neutrophils, TAMs, MDSCs, Tregs, and CAFs.
The development of cancer immunotherapies has been guided by advances in our understanding of the dynamics between tumor cells and immune populations. An emerging consensus is that immune control of tumors is mediated by cytotoxic CD8+ T cells, which directly recognize and kill tumor cells. The critical role of T cells in tumor control has been underscored by preclinical and clinical studies that observed that T cell presence is positively correlated with patient response to checkpoint blockade therapy. However, the vast majority of patients do not respond or develop resistance, frequently associated with exclusion of T cells from the tumor microenvironment. This review focuses on tumor cell-intrinsic alterations that blunt productive anti-tumor immune responses by directly or indirectly excluding effector CD8+ T cells from the tumor microenvironment. A comprehensive understanding of the interplay between tumors and the immune response holds the promise for increasing the response to current immunotherapies via the development of rational novel combination treatments.
Author Info: (1) Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, Cambridge, MA. Biology Department, Massachusetts Institute of Technology, Cambridge
Author Info: (1) Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, Cambridge, MA. Biology Department, Massachusetts Institute of Technology, Cambridge, MA. (2) Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, Cambridge, MA. Biology Department, Massachusetts Institute of Technology, Cambridge, MA.
