In recent years, the first-line available therapeutic options for metastatic renal cell carcinoma (mRCC) have radically changed with the introduction into clinical practice of new immune checkpoint inhibitor (ICI)-based combinations. Many efforts are focusing on identifying novel prognostic and predictive markers in this setting. The complement system (CS) plays a central role in promoting the growth and progression of mRCC. In particular, mRCC has been defined as an "aggressive complement tumor", which encompasses a group of malignancies with poor prognosie and highly expressed complement components. Several preclinical and retrospective studies have demonstrated the negative prognostic role of the complement in mRCC; however, there is little evidence on its possible role as a predictor of the response to ICIs. The purpose of this review is to explore more deeply the physio-pathological role of the complement in the development of RCC and its possible future use in clinical practice as a prognostic and predictive factor.
Keywords: biomarkers; classical pathway; complement; immunotherapy; mRCC; “aggressive complement” tumor.