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Nat Commun. 2019 Jun 18;10(1):2678. doi: 10.1038/s41467-019-10619-w.

Fcmr regulates mononuclear phagocyte control of anti-tumor immunity.

Author information

1
The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.
2
Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada.
3
Department of Immunology, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada.
4
The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. Tak.mak@uhnresearch.ca.
5
Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada. Tak.mak@uhnresearch.ca.
6
Department of Immunology, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada. Tak.mak@uhnresearch.ca.
7
Department of Medicine, University of Hong Kong, Pok Fu Lam, 999077, Hong Kong. Tak.mak@uhnresearch.ca.

Abstract

Myeloid cells contribute to tumor progression, but how the constellation of receptors they express regulates their functions within the tumor microenvironment (TME) is unclear. We demonstrate that Fcmr (Toso), the putative receptor for soluble IgM, modulates myeloid cell responses to cancer. In a syngeneic melanoma model, Fcmr ablation in myeloid cells suppressed tumor growth and extended mouse survival. Fcmr deficiency increased myeloid cell population density in this malignancy and enhanced anti-tumor immunity. Single-cell RNA sequencing of Fcmr-deficient tumor-associated mononuclear phagocytes revealed a unique subset with enhanced antigen processing/presenting properties. Conversely, Fcmr activity negatively regulated the activation and migratory capacity of myeloid cells in vivo, and T cell activation by bone marrow-derived dendritic cells in vitro. Therapeutic targeting of Fcmr during oncogenesis decreased tumor growth when used as a single agent or in combination with anti-PD-1. Thus, Fcmr regulates myeloid cell activation within the TME and may be a potential therapeutic target.

PMID:
31213601
PMCID:
PMC6581943
DOI:
10.1038/s41467-019-10619-w
[Indexed for MEDLINE]
Free PMC Article

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