In the so-called "antiangiogenic era" of recent years, a number of targeted therapies have been approved for the treatment of metastatic renal cell carcinoma (mRCC). Emerging information about the immunological features of mRCC and the immunomodulating properties of antiangiogenic agents, one of the standard treatments for mRCC, indicates that a more rational design of potentially synergistic combinations should be pursued. Indeed, immunotherapy has undergone a resurgence in clinical practice. In this narrative review, we discuss the immunological features of mRCC and the potential interactions that antiangiogenic agents may also exert on host immunity and tumor immunogenicity, possibly working on both sides of this complex cross-talk. Hence, the recall to Gianus, the ancient two-faced Roman God who was looking both at the future and the past. Treatment strategies will be also critically discussed.
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