Survival of the fittest: Cancer challenges T cell metabolism

Abstract T cells represent the major contributors to antitumor-specific immunity among the tumor-infiltrating lymphocytes. However, tumors acquire ways to evade immunosurveillance and anti-tumor responses are too weak to eradicate the disease. T cells are often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment, including stromal cells. Among these, nutrients use and consumption is critically important for the control of differentiation and effector mechanisms of T cells. Moreover, Treg cells-skewing conditions often coexist within the cancer milieu, which sustains the notion of immune privileged tumors. Additionally, cancer cells contend with tumor infiltrating lymphocytes for nutrients and can outcompete the immune response. PD1- and CTLA-based immunotherapies partially remodel cell metabolism leading the way to clinical approaches of metabolic reprogramming for therapeutic purposes. Here we shortly discuss T cell fates during anti-tumor immune responses and how signals within tumor microenvironment influence T cell metabolism, altering functions and longevity of the cell.