The complement system as a regulator of tumor-promoting activities mediated by myeloid-derived suppressor cells

Abstract

Tumor progression relies on the interaction between tumor cells and their surrounding tumor microenvironment (TME), which also influences therapeutic responses. The complement system, an essential part of innate immunity, has been traditionally considered an effector arm against tumors. However, established tumors co-opt complement-mediated immune responses in the TME to support chronic inflammation, activate cancer-related signaling pathways and hamper antitumor immune responses. In this context, myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid progenitors with immunosuppressive functions, are recognized as major mediators of tumor-associated complement activities. This review focuses on the impact of complement activation within the TME, with a special emphasis on MDSC functions and the involvement of the C5a/C5aR1 axis. We also discuss the translation of these findings into therapeutic advances based on complement inhibition.

Keywords: C5a; C5aR1; Cancer immunity; Complement system; Complement-derived fragments; Immunotherapy; Myeloid-derived suppressor cells; Tumor microenvironment.