Your browser doesn't support javascript.
loading
Immunotherapy-activated T cells recruit and skew late-stage activated M1-like macrophages that are critical for therapeutic efficacy.
van Elsas, Marit J; Middelburg, Jim; Labrie, Camilla; Roelands, Jessica; Schaap, Gaby; Sluijter, Marjolein; Tonea, Ruxandra; Ovcinnikovs, Vitalijs; Lloyd, Katy; Schuurman, Janine; Riesenfeld, Samantha J; Gajewski, Thomas F; de Miranda, Noel F C C; van Hall, Thorbald; van der Burg, Sjoerd H.
Affiliation
  • van Elsas MJ; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • Middelburg J; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • Labrie C; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • Roelands J; Department of Pathology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • Schaap G; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • Sluijter M; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • Tonea R; Department of Pathology, University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, Chicago, IL 60637, USA.
  • Ovcinnikovs V; Genmab, Utrecht 3584CT, the Netherlands.
  • Lloyd K; Genmab, Utrecht 3584CT, the Netherlands.
  • Schuurman J; Genmab, Utrecht 3584CT, the Netherlands.
  • Riesenfeld SJ; Pritzker School of Molecular Engineering, Chicago, IL 60637, USA.
  • Gajewski TF; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
  • de Miranda NFCC; Department of Pathology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • van Hall T; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
  • van der Burg SH; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden 2333ZA, the Netherlands. Electronic address: shvdburg@lumc.nl.
Cancer Cell ; 42(6): 1032-1050.e10, 2024 Jun 10.
Article in En | MEDLINE | ID: mdl-38759656
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.
Subject(s)
Key words

Full text: 1 Database: MEDLINE Main subject: CD8-Positive T-Lymphocytes / Immunotherapy / Macrophages Limits: Animals / Female / Humans Language: En Year: 2024 Type: Article

Full text: 1 Database: MEDLINE Main subject: CD8-Positive T-Lymphocytes / Immunotherapy / Macrophages Limits: Animals / Female / Humans Language: En Year: 2024 Type: Article