Fcmr regulates mononuclear phagocyte control of anti-tumor immunity

Shawn P. Kubli, Larsen Vornholz, Gordon Duncan, Wenjing Zhou, Parameswaran Ramachandran, Jerome Fortin, Maureen Cox, SeongJun Han, Robert Nechanitzky, Duygu Nechanitzky, Bryan E. Snow, Lisa Jones, Wanda Y. Li, Jillian Haight, Andrew Wakeham, Mark R. Bray and Tak W. Mak ()
Additional contact information
Shawn P. Kubli: Princess Margaret Cancer Centre
Larsen Vornholz: Princess Margaret Cancer Centre
Gordon Duncan: Princess Margaret Cancer Centre
Wenjing Zhou: Princess Margaret Cancer Centre
Parameswaran Ramachandran: Princess Margaret Cancer Centre
Jerome Fortin: Princess Margaret Cancer Centre
Maureen Cox: Princess Margaret Cancer Centre
SeongJun Han: Princess Margaret Cancer Centre
Robert Nechanitzky: Princess Margaret Cancer Centre
Duygu Nechanitzky: Princess Margaret Cancer Centre
Bryan E. Snow: Princess Margaret Cancer Centre
Lisa Jones: Princess Margaret Cancer Centre
Wanda Y. Li: Princess Margaret Cancer Centre
Jillian Haight: Princess Margaret Cancer Centre
Andrew Wakeham: Princess Margaret Cancer Centre
Mark R. Bray: Princess Margaret Cancer Centre
Tak W. Mak: Princess Margaret Cancer Centre

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10619-w

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