Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors.

ABSTRACT: Amyloid proteins are linked to various diseases; however, their functional roles in immunity and cancer remain unclear. Here, we establish a direct link between oligomeric cystatin C-a cysteine cathepsin inhibitor and a well-characterized amyloidogenic protein-within the tumor microenvironment and the immune inhibitory receptors LILRB2 and LILRB5 on myeloid cells. We demonstrated that human LILRB2 and LILRB5, along with their murine counterpart PIRB, serve as functional receptors for cystatin C oligomers. Engagement of these inhibitory receptors by oligomeric cystatin C enhances the immunosuppressive activity of myeloid cells, leading to T-cell suppression and tumor progression. Deletion of the CST3 gene, which encodes cystatin C, in host mice and tumor cells impaired tumor growth, whereas

SUBMITTER: Zhang C 

PROVIDER: S-EPMC12615798 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature