Complement inhibition in cancer therapy

Abstract

For decades, complement has been recognized as an effector arm of the immune system that contributes to the destruction of tumor cells. In fact, many therapeutic strategies have been proposed that are based on the intensification of complement-mediated responses against tumors. However, recent studies have challenged this paradigm by demonstrating a tumor-promoting role for complement. Cancer cells seem to be able to establish a convenient balance between complement activation and inhibition, taking advantage of complement initiation without suffering its deleterious effects. Complement activation may support chronic inflammation, promote an immunosuppressive microenvironment, induce angiogenesis, and activate cancer-related signaling pathways. In this context, inhibition of complement activation would be a therapeutic option for treating cancer. This concept is relatively new and deserves closer attention. In this article, we summarize the mechanisms of complement activation on cancer cells, the cancer-promoting effect of complement initiation, and the rationale behind the use of complement inhibition as a therapeutic strategy against cancer.

Keywords: AMD; Angiogenesis; C1 inhibitor; C1-INH; Cancer therapy; Complement system; Immunosuppression; Inflammation; MAC; MDSC; TGF-β; TLR; Tregs; Tumor microenvironment; age-related macular degeneration; membrane attack complex; myeloid-derived suppressor cells; regulatory T cells; toll-like receptor; transforming growth factor β.