Figure 4. Role of complement in cancer.

A complex interplay between complement effector proteins, tumor cells, and innate and adaptive immune cells in the tumor microenvironment determines tumor progression. Imbalanced complement activation in the tumor microenvironment triggers the release of proinflammatory cytokines by both tumor cells and tumor-infiltrating immune cells, such as macrophages, dendritic cells, and neutrophils, as well as immunosuppressive cytokines and reactive oxygen and nitrogen species by myeloid-derived suppressor cells (MDSCs). Local inflammation suppresses activation of effector T cells and creates a favorable environment for tumor growth. MDSCs also exert potent immunosuppressive effects that inhibit anti-tumor CD8⁺ T cell responses. Complement activation products, particularly C5a, promotes angiogenesis, thus facilitating tumor cell migration and adjacent tissue invasion and metastasis. Complement activation also triggers the accumulation of pro-tumorigenic neutrophils within solid tumors potentiating their procoagulant responses by releasing neutrophil extracellular traps (NETs).