Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression.

ABSTRACT: Complement has emerged as a component of tumor promoting inflammation. We conducted a systematic assessment of the role of complement activation and effector pathways in sarcomas. C3^-/-, MBL1/2^-/- and C4^-/- mice showed reduced susceptibility to 3-methylcholanthrene sarcomagenesis and transplanted sarcomas, whereas C1q and factor B deficiency had marginal effects. Complement 3a receptor (C3aR), but not C5aR1 and C5aR2, deficiency mirrored the phenotype of C3^-/- mice. C3 and C3aR deficiency were associated with reduced accumulation and functional skewing of tumor-associated macrophages, increased T cell activation and response to anti-PD-1 therapy. Transcriptional profiling of sarcoma infiltrating macrophages and monocyt

SUBMITTER: Magrini E 

PROVIDER: S-EPMC8425276 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature