Immunotherapy-activated T cells recruit and skewlate-stage activated M1-like macrophagesthat are critical for therapeutic efficacy
Cancer Cell(2024)
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 skewed 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.
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Key words
cancer immunotherapy,T cell-macrophage interactions,coordinated immunity,effector macrophages,M1 macrophages,CCR5 attraction,macrophage skewing,CXCL9/CXCL10,immune checkpoint inhibition
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