Spatiotemporal co-dependency between macrophages and exhausted CD8⁺ T cells in cancer.

ABSTRACT: T cell exhaustion is a major impediment to antitumor immunity. However, it remains elusive how other immune cells in the tumor microenvironment (TME) contribute to this dysfunctional state. Here, we show that the biology of tumor-associated macrophages (TAMs) and exhausted T cells (T_ex) in the TME is extensively linked. We demonstrate that in vivo depletion of TAMs reduces exhaustion programs in tumor-infiltrating CD8⁺ T cells and reinvigorates their effector potential. Reciprocally, transcriptional and epigenetic profiling reveals that T_ex express factors that actively recruit monocytes to the TME and shape their differentiation. Using lattice light sheet microscopy, we show that TAM and CD8⁺ T cells engage in unique, long-lasting, antigen-speci

SUBMITTER: Kersten K 

PROVIDER: S-EPMC9197962 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature