Peripheral γδ T-lymphocytes as an innovative tool in immunotherapy for metastatic renal cell carcinoma

Renal cell carcinoma represents 3% of solid malignancies in adults and nephrectomy remains the main treatment. Failure of conventional approaches for patients presenting with advanced disease has prompted the exploration of new strategies. This review describes the potential use of peripheral gammadelta (Vgamma9Vdelta2) T-cells in metastatic renal cell carcinoma. This peripheral lymphocyte population from the innate immune system has demonstrated an in vitro antitumor cytotoxicity against primary or established renal cell lines. Moreover, these Vgamma9Vdelta2 lymphocytes undergo a rapid and extensive expansion in vitro as well as in vivo upon stimulation with a synthetic potent agonist, the bromohydrin pyrophosphate molecule. Preclinical results obtained on specific in vitro amplification of Vgamma9Vdelta2 T-cells by bromohydrin pyrophosphate in renal cell carcinoma patients are presented in this review, while Phase I clinical trials are currently running. As there is growing evidence for the low efficiency of monotherapy in cancer patients, innovative approaches combining immunomodulatory gammadelta agonists with classic chemotherapies or administration of antiangiogenic agents are discussed.