Søren Kragh Moestrup

Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression

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  • Anders Etzerodt
  • Kyriaki Tsalkitzi, CNRS, Aix Marseille University, INSERM, CIML, Marseille 13009, France.
  • ,
  • Maciej Maniecki, Department of Dermatology, Yale University School of Medicine, New Haven, CT.
  • ,
  • William Damsky, Department of Dermatology, Yale University School of Medicine, New Haven, CT.
  • ,
  • Marcello Delfini, CNRS, Aix Marseille University, INSERM, CIML, Marseille 13009, France.
  • ,
  • Elodie Baudoin, CNRS, Aix Marseille University, INSERM, CIML, Marseille 13009, France.
  • ,
  • Morgane Moulin, Centre for Inflammation Biology and Cancer Immunology, School of Immunology and Microbial Sciences, King's College London, London, UK.
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  • Marcus Bosenberg, Department of Dermatology, Yale University School of Medicine, New Haven, CT.
  • ,
  • Jonas Heilskov Graversen, University of Southern Denmark
  • ,
  • Nathalie Auphan-Anezin, CNRS, Aix Marseille University, INSERM, CIML, Marseille 13009, France.
  • ,
  • Søren Kragh Moestrup
  • Toby Lawrence, CNRS, Aix Marseille University, INSERM, CIML, Marseille 13009, France; Centre for Inflammation Biology and Cancer Immunology, School of Immunology & Micriboal Sciences, King's College London, London SE1 1UL, UK; Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, China. Electronic address: toby.lawrence@kcl.ac.uk.

Tumor-associated macrophages (TAMs) play critical roles in tumor progression but are also capable of contributing to antitumor immunity. Recent studies have revealed an unprecedented heterogeneity among TAMs in both human cancer and experimental models. Nevertheless, we still understand little about the contribution of different TAM subsets to tumor progression. Here, we demonstrate that CD163-expressing TAMs specifically maintain immune suppression in an experimental model of melanoma that is resistant to anti-PD-1 checkpoint therapy. Specific depletion of the CD163+ macrophages results in a massive infiltration of activated T cells and tumor regression. Importantly, the infiltration of cytotoxic T cells was accompanied by the mobilization of inflammatory monocytes that significantly contributed to tumor regression. Thus, the specific targeting of CD163+ TAMs reeducates the tumor immune microenvironment and promotes both myeloid and T cell-mediated antitumor immunity, illustrating the importance of selective targeting of tumor-associated myeloid cells in a therapeutic context.

Original languageEnglish
JournalThe Journal of Experimental Medicine
Volume216
Issue10
Pages (from-to)2394-2411
Number of pages18
ISSN0022-1007
DOIs
Publication statusPublished - 7 Oct 2019

    Research areas

  • BLOCKADE, EXPRESSION, HEMOGLOBIN, INDUCE, IPILIMUMAB, LIPOSOMES, MACROPHAGES, MELANOMA, MICROENVIRONMENT, MYELOID CELLS

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