Immunological effects and therapeutic role of C5a in cancer

Abstract

The specific role of C5a in cancer, especially in melanoma, has yet to be determined. Differential effects of C5a could be cancer specific. In the host defense system, C5a functions to protect the body from harmful entities via a plethora of mechanisms. Yet, C5a may also serve to potentiate cancerous process. C5a facilitates cellular proliferation and regeneration by attracting myeloid-derived suppressor cells and supporting tumor promotion. In this article, we critically reviewed the properties, mechanisms of action and functions of C5a, with particular emphasis on cancer inhibition and promotion, and clinical application of such knowledge in better management of patients with cancer. Outstanding questions and future directions in regard to the function of C5a in melanoma and other cancers are discussed.

Keywords:

• C5a
• cancer
• chronic inflammation
• complement
• immunosuppression
• melanoma

Disclaimer

The content of this review is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Financial & competing interest disclosure

This work was supported by research grants from the NIH, USA, to DK Agrawal. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the article apart from those disclosed.

No writing assistance was used in the production of this article.

Key issues

• If the concentration of C5a determines its antitumorigenic or tumorigenic effect, what is the threshold concentration?

• Is the effect of C5a in various concentrations dependent on the tumor microenvironment and cancer type?

• Studies are required to completely elucidate the underlying mechanisms of the antitumorigenic or protumorigenic effects of C5a.

• The comparative role of C5a receptors, CD88 and C5L2 in tumor invasiveness and tumor progression needs further investigation.

• What is the mechanism by which C5a stimulates VEGF release?

• What is the effect of proinflammatory cytokines in angiogenesis induced by the interaction between C5a and VEGF?

Notes