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J Exp Med. 2019 Aug 2. pii: jem.20182124. doi: 10.1084/jem.20182124. [Epub ahead of print]

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

Author information

1
Aix Marseille University, CNRS, INSERM, CIML, Marseille, France ae@biomed.au.dk.
2
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
3
Aix Marseille University, CNRS, INSERM, CIML, Marseille, France.
4
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
5
Department of Dermatology, Yale University School of Medicine, New Haven, CT.
6
Centre for Inflammation Biology and Cancer Immunology, School of Immunology and Microbial Sciences, King's College London, London, UK.
7
Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
8
Aix Marseille University, CNRS, INSERM, CIML, Marseille, France toby.lawrence@kcl.ac.uk.
9
Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.

Abstract

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.

PMID:
31375534
DOI:
10.1084/jem.20182124

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