Microenvironment-driven metabolic adaptations guiding CD8⁺ T cell anti-tumor immunity

The metabolic stress occurring in the tumor microenvironment (TME) hampers T cell anti-tumor immunity by disturbing T cell metabolic and epigenetic programs. Recent studies are making headway toward identifying strategies to unleash T cell activities by targeting T cell metabolism. Furthermore, efforts have been made to improve the efficacy of immune checkpoint blockade and adoptive cell transfer therapies. However, distinct treatment outcomes across different cancers raise the question of whether our understanding of the features of CD8⁺ T cells within the TME are universal, regardless of their tissue of origin. Here, we review the common and distinct environmental factors affecting CD8⁺ T cells across tumors. Moreover, we discuss how distinct tissue-specific niches are interpreted by CD8⁺ T cells based on studies on tissue-resident memory T (Trm) cells and how these insights can pave the way for a better understanding of the metabolic regulation of CD8⁺ T cell differentiation and anti-tumor immunity.