Targeting T Cell Immunometabolism for Cancer Immunotherapy; Understanding the Impact of the Tumor Microenvironment

Mary B. Mockler, Melissa J. Conroy, Joanne Lysaght

The immune system has a key role to play in controlling cancer initiation and progression. T cell activation, which is central to anti-tumor immune responses, coincides with changes in cellular metabolism. Naïve T cells predominantly require an ATP generating metabolic profile, whereas proliferating effector T cells require anabolic metabolic profiles that promote rapid growth and proliferation. Furthermore, specific T cell subsets require distinct energetic and biosynthetic pathways to match their functional requirements. The often hostile tumor microenvironment can affect T cell immune responses by altering the resulting cellular metabolism. Tailoring immune responses by manipulating cellular metabolic pathways may provide an exciting new option for cancer immunotherapy. T cell responses might also be skewed via metabolic manipulation to treat the complications of obesity-associated inflammation, which is a rapidly growing global health problem and a major risk factor for many malignancies. In this review, the diverse metabolic requirements of T cells in anti-tumor immunity are discussed, as well as the profound influence of the tumor microenvironment and the possible avenues for manipulation to enhance anti-tumor immunity.