Complement C5a Fosters Squamous Carcinogenesis and Limits T Cell Response to Chemotherapy.

ABSTRACT: Complement is a critical component of humoral immunity implicated in cancer development; however, its biological contributions to tumorigenesis remain poorly understood. Using the K14-HPV16 transgenic mouse model of squamous carcinogenesis, we report that urokinase (uPA)⁺ macrophages regulate C3-independent release of C5a during premalignant progression, which in turn regulates protumorigenic properties of C5aR1⁺ mast cells and macrophages, including suppression of CD8⁺ T cell cytotoxicity. Therapeutic inhibition of C5aR1 via the peptide antagonist PMX-53 improved efficacy of paclitaxel chemotherapy associated with increased presence and cytotoxic properties of CXCR3⁺ effector memory CD8⁺ T cells in carcinomas, dependent on both macrop

SUBMITTER: Medler TR 

PROVIDER: S-EPMC6246036 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature