Complement and the hallmarks of cancer
Mikel Rezola Artero, Andrea Minery, Leon Nedelcev, Maria Radanova, Lubka T. Roumenina
Abstract
The hallmarks of cancer are a set of traits that normal cells acquire during their transformation into malignancy. Among the biological processes influencing these hallmarks, the innate immune complement system plays a critical role. It can operate canonically-in blood and tissues-via phagocytosis, inflammation, and complement-dependent cytotoxicity, similar to its roles against invading pathogens. Additionally, it functions non-canonically by modulating the behavior of cells within the tumor microenvironment and their intracellular landscape which regulates cell fate. These mechanisms contribute to the complex and context-dependent roles of complement in both tumor growth and antitumor immunity, shaped by the characteristics of the dynamic tumor microenvironment. This review analyses the multifaceted interplay between complement proteins and cancer hallmarks, positioning this system as a target to cancer therapy.