Metabolite-driven antitumor immunity

 JAMES A. NATHAN

DOI: 10.1126/science.ade3697

Abstract

Otto Warburg’s observations that solid organ tumors preferentially use aerobic glycolysis, metabolizing glucose to lactate, to facilitate growth paved the way for our understanding of how nutrient availability and metabolism can promote cancer. A common theme is that proliferating tumor cells use a diverse array of mechanisms to acquire nutrients to grow rather than to simply support adenosine triphosphate (ATP) production (1). However, promoting cell growth is generally not sufficient for solid-organ tumors to develop because they must also evade cytotoxic T cells, raising the question of whether this immune evasion is linked to metabolism. On page 1519 of this issue, Notarangelo et al. (2) show that D-2-hydroxyglutarate (D-2HG), a metabolite secreted by tumors with mutations in isocitrate dehydrogenase (IDH) (3), functions within the tumor microenvironment (TME) to impair CD8+ T cell–mediated tumor cell killing. These findings highlight the potential for metabolites within the TME to alter antitumor immune responses.

https://www.science.org/doi/10.1126/science.ade3697