UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment.

ABSTRACT: Dysregulation of the C5a-C5a receptor 1 (C5aR1) signalling axis underlies inflammation and immune-driven pathology. C5aR1 was traditionally thought to be primarily expressed on the cell membrane, although recent reports indicate the importance of intracellular C5aR1 expression for the inflammatory effector functions of various cell types. However, the mechanisms regulating C5aR1 expression and localisation remain unclear. In tumours with an immunosuppressive microenvironment, we recently found C5aR1 expression on malignant epithelial cells, highlighting potential tumour cell-specific functions. Here, we show that physical conditions of the tumour microenvironment leading to immunosuppression, induce C5aR1 expression and control its intracellular localisation. Mechanistically, we find that

SUBMITTER: Suwa T 

PROVIDER: S-EPMC12284258 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature