Moreover, the strong involvement of complement system in the ccRCC microenvironment strongly support the idea that PTX3 up-regulation modulates the effector routes associated with the cancer-immunity cycle, providing the rationale for new therapeutic combinations aimed to enhance the antitumor efficacy of anti-PD-1/PD-L1 checkpoint inhibitors in this neoplasia. This evidence concerns the gene PTX3 and nonpapillary renal cell carcinoma.