The Complement System in Ovarian Cancer: An Underexplored Old Path.

Ovarian cancer is one of the most lethal gynecological cancers. Current therapeutic strategies allow temporary control of the disease, but most patients develop resistance to treatment. Moreover, although successful in a range of solid tumors, immunotherapy has yielded only modest results in ovarian cancer. Emerging evidence underscores the relevance of the components of innate and adaptive immunity in ovarian cancer progression and response to treatment. Particularly, over the last decade, the complement system, a pillar of innate immunity, has emerged as a major regulator of the tumor microenvironment in cancer immunity. Tumor-associated complement activation may support chronic inflammation, promote an immunosuppressive microenvironment, induce angiogenesis, and activate cancer-related signaling pathways. Recent insights suggest an important role of complement effectors, such as C1q or anaphylatoxins C3a and C5a, and their receptors C3aR and C5aR1 in ovarian cancer progression. Nevertheless, the implication of these factors in different clinical contexts is still poorly understood. Detailed knowledge of the interplay between ovarian cancer cells and complement is required to develop new immunotherapy combinations and biomarkers. In this context, we discuss the possibility of targeting complement to overcome some of the hurdles encountered in the treatment of ovarian cancer.