Renal Cell Carcinoma (RCC) is the most common tumor originating from the kidneys.
In comparison to other solid tumors, RCC is poorly sensitive to conventional therapeutic modalities.
As such, metastatic RCC (mRCC) continues to be associated with high rates of morbidity and
mortality. Targeted agents have shown remarkable progress in RCC management with improved
patients’ outcomes, but rarely induce complete response and patients develop resistance to therapy
eventually. However, it is well known that RCC represents one of the most immunogenic cancers
and is able to evoke immune response naturally, thus prompted the emergence of several immunotherapeutic
strategies in the management of RCC with variable degrees of success. Modulating the
immune system with cytokines, vaccines, and T-cell modulating agents offer hope for the patients
with RCC. High-dose Interleukin-2 (IL-2) still remains an appropriate first-line treatment for selected
patients and is associated with durable complete remissions in a small fraction of treated
patients. RCC vaccines have much less toxicity than other current therapeutic agents and remain an
important area for further research, for example, Oncophage and Reniale, the two representative
RCC vaccines, have shown significant benefits as an adjuvant treatment for RCC. Immune checkpoint
inhibitors are evolving rapidly due to the increased understanding of the genetic and metabolic
basis of tumors. In particular, Nivolumab is the most completely characterized antiprogrammed
cell death 1 (anti-PD-1) agent in RCC and even has been shown to be efficacious as
monotherapy with mRCC following a failed antiangiogenic therapy. This review critically summarizes
the state of the art in RCC therapeutic regimen with immunomodulation agents. We will focus
on the clinical data and ongoing clinical trials exploring the use of immunotherapy with different
agents for RCC. In addition, different novel immunotherapeutic agents are being investigated for
their combination therapy with other immune therapies or other modalities. Prospects (e.g., potential
future immunological targets, combination regimens, appropriate sequencing) for immune
therapies of RCC are also set forth in this review.