MTOR-dependent immunometabolism as Achilles' heel of anticancer therapy.

Abstract

Immune cells are important constituents of the tumor microenvironment and essential in eradicating tumor cells during conventional therapies or novel immunotherapies. The mechanistic target of rapamycin (mTOR) signaling pathway senses the intra- and extracellular nutrient status, growth factor supply, and cell stress-related changes to coordinate cellular metabolism and activation dictating effector and memory functions in mainly all hematopoietic immune cells. In addition, the mTOR complex 1 (mTORC1) and mTORC2 are frequently deregulated and become activated in cancer cells to drive cell transformation, survival, neovascularization, and invasion. In this review, we provide an overview of the influence of mTOR complexes on immune and cancer cell function and metabolism. We discuss how mTOR inhibitors aiming to target cancer cells will influence immunometabolic cell functions participating either in antitumor responses or favoring tumor cell progression in individual immune cells. We suggest immunometabolism as the weak spot of anticancer therapy and propose to evaluate patients according to their predominant immune cell subtype in the cancer tissue. Advances in metabolic drug development that hold promise for more effective treatments in different types of cancer will have to consider their effects on the immune system.