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Publication : Immunotherapy-activated T cells recruit and skew late-stage activated M1-like macrophages that are critical for therapeutic efficacy.

First Author  van Elsas MJ Year  2024
Journal  Cancer Cell Volume  42
Issue  6 Pages  1032-1050.e10
PubMed ID  38759656 Mgi Jnum  J:349430
Mgi Id  MGI:7646765 Doi  10.1016/j.ccell.2024.04.011
Citation  van Elsas MJ, et al. (2024) Immunotherapy-activated T cells recruit and skew late-stage activated M1-like macrophages that are critical for therapeutic efficacy. Cancer Cell
abstractText  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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