Targeting T cell metabolism for therapy

Abstract

In the past several years, a wealth of evidence has emerged illustrating how metabolism supports many aspects of T cell biology, as well as how metabolic changes drive T cell differentiation and fate. Here we outline developing principles in the regulation of T cell metabolism, and discuss how these processes are impacted in settings of inflammation and cancer. In this context we discuss how metabolic pathways might be manipulated for the treatment of human disease, including how metabolism may be targeted to prevent T cell dysfunction in inhospitable microenvironments, to generate more effective adoptive cellular immunotherapies in cancer, and to direct T cell differentiation and function towards non-pathogenic phenotypes in settings of autoimmunity.

Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma

“…Mechanisms of this therapeutic resistance are poorly understood. It is clear that effector T cells require metabolic reprogramming for maximal function (50). Here we show, however, that ccRCC CD8 TIL have multiple metabolic impairments that contribute to limited activation.…”

Antibiotic Overusage Causes Mitochondrial Dysfunction Which May Promote Tumorigenesis

“…This co-metabolism can determine the result of immunotherapeutics and cancer cell survival [12][13][14]. Certain bacterial species of the microbiota play important roles in modulating the host immune system.…”

Oxidative Stress and Metabolism

“…A novel approach to cancer therapy is to change the metabolism of cancers, so that the nutrient microenvironment favors T effectors rather than Tregs. 27,28 Consistent with the above hypothesis is the observation that targeted mutation of mTOR, which is common to both the mTORC1 and mTORC2 pathways, directs T lymphocytes toward a Treg phenotype. 25 However, the effects of individually mutating specific components of either the mTORC1 and/or mTORC2 pathways are complex.…”