Chemokines that govern T cell activity in tumors

Local regulation of T cell-mediated immunity to solid tumors occurs at multiple levels, including their recruitment from the bloodstream to the tumor microenvironment (TME), coordinated crosstalk with different subsets of antigen-presenting cells (APCs) controlling their local survival, proliferation, and effector differentiation, as well as their egress from tumors via lymphatics. At each level, chemokines play essential roles, for instance, by guiding directional T cell migration across blood and lymphatic endothelial barriers or by promoting their spatial proximity and direct physical interactions with APCs to enable functional crosstalk. In this article, we will review recent mechanistic insights into the chemokine axes that guide T cell functions in TMEs in light of the emerging functional state heterogeneity of CD8⁺ effector T cells and our growing understanding of how regulatory T cells restrain antitumor activity.