下调和上调
细胞生物学
PI3K/AKT/mTOR通路
免疫系统
生物
蛋白激酶B
单核细胞
巨噬细胞
受体
癌症研究
信号转导
免疫学
体外
生物化学
基因
作者
Sarah Sutherland,Xinsheng Ju,Pablo A. Silveira,Fiona Kupresanin,Lisa G. Horvath,Georgina J. Clark
标识
DOI:10.1016/j.cellimm.2023.104731
摘要
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.
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