CD300f signalling induces inhibitory human monocytes/macrophages

Sarah I M Sutherland; Xinsheng Ju; Pablo A Silveira; Fiona Kupresanin; Lisa G Horvath; Georgina J Clark

doi:10.1016/j.cellimm.2023.104731

CD300f signalling induces inhibitory human monocytes/macrophages

Cell Immunol. 2023 Aug:390:104731. doi: 10.1016/j.cellimm.2023.104731. Epub 2023 Jun 2.

Authors

Sarah I M Sutherland¹, Xinsheng Ju², Pablo A Silveira², Fiona Kupresanin³, Lisa G Horvath⁴, Georgina J Clark⁵

Affiliations

¹ Dendritic Cell Research, ANZAC Research Institute, Sydney, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Chris O'Brien Lifehouse, Sydney, NSW, Australia.
² Dendritic Cell Research, ANZAC Research Institute, Sydney, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
³ Dendritic Cell Research, ANZAC Research Institute, Sydney, NSW, Australia.
⁴ Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Chris O'Brien Lifehouse, Sydney, NSW, Australia; Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁵ Dendritic Cell Research, ANZAC Research Institute, Sydney, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. Electronic address: georgina.clark@sydney.edu.au.

PMID: 37302321
DOI: 10.1016/j.cellimm.2023.104731

Abstract

The CD300 glycoproteins are a family of related leucocyte surface molecules that regulate the immune response via their paired triggering and inhibitory receptors. Here we studied CD300f, an apoptotic cell receptor, and how it modulates the function of human monocytes and macrophages. We showed that CD300f signalling by crosslinking with anti-CD300f mAb (DCR-2) suppressed monocytes causing upregulation of the inhibitory molecule, CD274 (PD-L1) and their inhibition of T cell proliferation. Furthermore, CD300f signalling drove macrophages preferentially towards M2-type with upregulation of CD274, which was further enhanced by IL-4. CD300f signalling activates the PI3K/Akt pathway in monocytes. Inhibition of PI3K/Akt signalling resulting from CD300f crosslinking leads to downregulation of CD274 expression on monocytes. These findings highlight the potential use of CD300f blockade in cancer immune therapy to target immune suppressive macrophages in the tumour microenvironment, a known resistance mechanism to PD-1/PD-L1 checkpoint inhibitors.

Keywords: CD300f; Checkpoint inhibitors; Macrophages; Monocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen* / metabolism
Humans
Macrophages
Monocytes*
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Receptors, Immunologic / metabolism

Substances

B7-H1 Antigen
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Receptors, Immunologic
CD300LF protein, human