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Immunotherapy-activated T cells install a subset of late-stage activated M1-like macrophages that are critical for therapeutic efficacy

ABSTRACT: Total tumor clearance through immunotherapy is associated with a fully coordinated innate and adaptive immune response, but knowledge on the exact contribution of each immune cell subset is limited. We show that therapy-induced intratumoral CD8 T cells recruited and installed late-stage activated M1-like macrophages, which were critical for effective tumor control in two different murine models of cancer immunotherapy. The activated CD8 T cells summon these macrophages into the tumor and their close vicinity via CCR5-signaling. Exposure of non-polarized macrophages to activated T-cell supernatant and tumor lysate recapitulates the late-stage activated and tumoricidal phenotype in vitro.The transcriptomic signature of these macrophages is also detected in a similar macrophage population present in human tumors and coincides with clinical response to immune checkpoint inhibitors. The requirement of a functional co-operation between CD8 T cells and effector macrophages for effective immunotherapy gives warning to combinations with broad macrophage targeting strategies.

ORGANISM(S): Mus musculus

PROVIDER: GSE263235 | GEO | 2024/06/10

REPOSITORIES: GEO

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