Clinical observations of spontaneous disease regression in some renal cell carcinoma (RCC) patients implicate a role for tumor immunity in controlling this disease. Puzzling, however, are findings that high levels of tumor infiltrating lymphocytes (TIL) are common to RCC. Despite expression of activation markers by TILs, functional impairment of innate and adaptive immune cells has been consistently demonstrated contributing to the failure of the immune system to control RCC. Immunotherapy can overcome the immunosuppressive effects of the tumor and provide an opportunity for long-term disease free survival. Unfortunately, complete response rates remain sub-optimal indicating the effectiveness of immunotherapy remains limited by tumor-specific factors and/or cell types that inhibit antitumor immune responses. Here we discuss immunotherapies and the function of multiple immune system components to achieve an effective response. Understanding these complex interactions is essential to rationally develop novel therapies capable of renewing the immune system's ability to respond to these tumors.
Bibliographical noteFunding Information:
This work was supported by grants from the National Institute of Child Health and Human Development (R15HD073868; D.S.T.) and National Cancer Institute (R15CA173657; D.S.T. and A.W.), (R01CA109446; T.S.G.). The funders had no role in preparation of the manuscript or decision to publish.
- NK cell
- Renal cell carcinoma
- T cell