Activated lymphocytes as a metabolic model for carcinogenesis

The mid-twentieth century has been described as the ‘golden age of intermediary metabolism’ [1], with the work of Krebs, Lippman, Crane and others greatly advancing our understanding of cellular metabolic pathways. In the past decade interest in cell metabolism has been rejuvenated in several fields, especially cancer biology and lymphocyte immunology. In cancer biology, this renaissance has been driven by evidence that cancer metabolism presents an underexploited therapeutic target. Immunologists have been drawn to metabolic studies with the realization that the metabolism of T lymphocytes (T cells) is intimately tied to immunity [2]. Functionally, T cells and tumors have little in common; the former protects against invasive pathogens, the latter is a diseased tissue characterized by the accumulation of abnormal cells. However, both T cells and cancer cells have strong proliferative signals and undergo metabolic reprogramming during their respective life cycles, and there exist clear functional and mechanistic similarities between the reprogramming events in each cell type. These similarities make lymphocyte metabolic reprogramming a useful model with which to discover how and why tumors rewire their metabolism. The purpose of this review is to highlight and discuss the similarities and distinctions in how T cells and tumor cells solve similar metabolic problems.Because of its inherently destructive nature, the immune system must be maintained in a quiescent state. To provide protection from pathogens, however, it must remain capable of rapid responses and effector function. This challenge is solved with a diverse pool of na？ve lymphocytes that can quickly activate to produce a large, clonal pool of rapidly proliferating effector T cells. Na？ve T cells express near-unique T cell antigen receptors (TCR) that are randomly generated through V(D)J recombination and pre-selected to recognize foreign antigens presented on major histocompatibility complexes (MHC). These