Intrinsic immune alterations in renal cell carcinoma and emerging immunotherapeutic approaches

Introduction: Individuals affected by kidney cancer present a variety of immune abnormalities including cellular immune dysfunction, cytokine alterations and antigen presentation defects. On the other hand, spontaneous remissions are seen in up to 4% of renal cell carcinoma (RCC) patients and they are thought to occur via immune mechanisms. Areas covered: The authors comprehensively review the immune abnormalities in RCC patient and describe the kidney cancer immunotherapy candidates that are most advanced in their clinical development. Most relevant publications were identified through searching the PubMed database; the obtained information was thoroughly analyzed and synthesized. Expert opinion: As cure in advanced RCC cannot be accomplished with the current therapy standards such as tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, new treatment strategies are being sought. Enhancing the immune system represents an appealing avenue for kidney cancer therapy. Disappointingly, high-dose interleukin-2 and interferon-alpha cause severe toxicity and produce a questionable clinical benefit. The authors postulate that the 'durable responses' seen with these agents in only a handful of RCC patients represent spontaneous remissions. Promising immune strategies in RCC such as anti-cytotoxic T-lymphocyte-associated protein antibodies, anti-programmed cell death 1 (PD1)/PD1 ligand and tumor vaccines may expand the existing options for kidney cancer in future years.