2. Academic Validation
  3. Immunotherapy-activated T cells recruit and skew late-stage activated M1-like macrophages that are critical for therapeutic efficacy

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

  • Cancer Cell. 2024 May 16:S1535-6108(24)00135-1. doi: 10.1016/j.ccell.2024.04.011.
Marit J van Elsas 1,  Jim Middelburg 1,  Camilla Labrie 1,  Jessica Roelands 2,  Gaby Schaap 1,  Marjolein Sluijter 1,  Ruxandra Tonea 3,  Vitalijs Ovcinnikovs 4,  Katy Lloyd 4,  Janine Schuurman 4,  Samantha J Riesenfeld 5,  Thomas F Gajewski 6,  Noel F C C de Miranda 2,  Thorbald van Hall 1,  Sjoerd H van der Burg 7
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • 2 Department of Pathology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • 3 Department of Pathology, University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, Chicago, IL 60637, USA.
  • 4 Genmab, Utrecht 3584CT, the Netherlands.
  • 5 Pritzker School of Molecular Engineering, Chicago, IL 60637, USA.
  • 6 Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
  • 7 Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands. Electronic address: shvdburg@lumc.nl.
PMID: 38759656 DOI: 10.1016/j.ccell.2024.04.011
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.

Keywords

CCR5 attraction; CXCL9/CXCL10; M1 macrophages; T cell-macrophage interactions; cancer immunotherapy; coordinated immunity; effector macrophages; immune checkpoint inhibition; macrophage skewing.

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