Complement System: Promoter or Suppressor of Cancer Progression?

Abstract

Constituent of innate immunity, complement is present in the tumor microenvironment. The functions of complement include clearance of pathogens and maintenance of homeostasis, and as such could contribute to an anti-tumoral role in the context of certain cancers. However, multiple lines of evidence show that in many cancers, complement has pro-tumoral actions. The large number of complement molecules (over 30), the diversity of their functions (related or not to the complement cascade), and the variety of cancer types make the complement-cancer topic a very complex matter that has just started to be unraveled. With this review we highlight the context-dependent role of complement in cancer. Recent studies revealed that depending of the cancer type, complement can be pro or anti-tumoral and, even for the same type of cancer, different models presented opposite effects. We aim to clarify the current knowledge of the role of complement in human cancers and the insights from mouse models. Using our classification of human cancers based on the prognostic impact of the overexpression of complement genes, we emphasize the strong potential for therapeutic targeting the complement system in selected subgroups of cancer patients.

C8B in Complement and Coagulation Cascades Signaling Pathway is a predictor for Survival in HBV-Related Hepatocellular Carcinoma Patients

“…The functions of complement could be anti-tumoral and pro-tumoral depending on the cancer type, even for the same type of cancer. 33,34 As a member of the complement gene family, complement C8 consists of three subunits encoded by individual genes: C8A, C8B, and C8G. C8 serves as a main component of the membrane attack complex.…”

Complement 4 Aids in Prediction of Newly Diagnosed Multiple Myeloma Outcome in Patients

“…Complement components are mainly produced by the liver, but It is worth noting that some tumor cells and stromal cells also have the ability to produce complement proteins. Therefore, in different tumor types, complement may be anti-tumor or pro-tumor; despite the sameness of the tumor type, a slew of complement effects can be expected [19].…”

Special Issue: The Role of Complement in Cancer Immunotherapy

“…The complement system plays an important role in critical aspects of immune defense and in the maintenance of homeostasis in the bloodstream, as well as in essentially all tissues and organs [1]. More than 100 years ago, Bordet was awarded the Nobel Prize for his discovery of complement.…”

“…In terms of maintaining homeostasis, complement promotes wound healing and angiogenesis (essential to cell growth) and there is a substantial literature that describes how complement can establish an environment that allows for growth of tumors. This is most evident when the tumors are not recognized as foreign, and therefore can take advantage of the "cell growth"-promoting action of complement [1,5]. The encyclopedic review of Revel and colleagues comprehensively describes complement pathways as well as the numerous cases in which specific complement components, especially C1q and C5a, play important roles both in promoting tumor growth and in generating an immunosuppressive environment [1].…”

“…This is most evident when the tumors are not recognized as foreign, and therefore can take advantage of the "cell growth"-promoting action of complement [1,5]. The encyclopedic review of Revel and colleagues comprehensively describes complement pathways as well as the numerous cases in which specific complement components, especially C1q and C5a, play important roles both in promoting tumor growth and in generating an immunosuppressive environment [1]. Weak immune responses to the tumors (titers of IgG and IgM insufficient to mediate cell killing) appear to activate and recruit complement proteins to foster cell growth, and the complement components can be produced by the host or generated by the tumors themselves.…”