Complement in Tumourigenesis and the Response to Cancer Therapy

SIMPLE SUMMARY: Increasing evidence supports a role for complement in the development of cancer and the response to cancer treatments. Dysregulated complement expression within the tumour microenvironment has been linked to the suppression of anti-tumour immunity and poor clinical outcomes. Complement signals have been demonstrated to alter the immune milieu, promote proliferation and facilitate metastasis. Targeting complement signalling in combination with current treatments may have the potential to achieve improved control of tumour growth. ABSTRACT: In recent years, our knowledge of the complement system beyond innate immunity has progressed significantly. A modern understanding is that the complement system has a multifaceted role in malignancy, impacting carcinogenesis, the acquisition of a metastatic phenotype and response to therapies. The ability of local immune cells to produce and respond to complement components has provided valuable insights into their regulation, and the subsequent remodeling of the tumour microenvironment. These novel discoveries have advanced our understanding of the immunosuppressive mechanisms supporting tumour growth and uncovered potential therapeutic targets. This review discusses the current understanding of complement in cancer, outlining both direct and immune cell-mediated roles. The role of complement in response to therapies such as chemotherapy, radiation and immunotherapy is also presented. While complement activities are largely context and cancer type-dependent, it is evident that promising therapeutic avenues have been identified, in particular in combination therapies.