Roberto Iacovelli, MD, is a medical oncologist at University Hospital of Verona in Italy. An authority on kidney cancer treatment, Dr Iacovelli coauthored a recent paper in Expert Opinion on Biology Therapy exploring the future of personalized immunotherapy for patients with renal cell carcinoma (RCC).1
In this question-and-answer session, Cancer Therapy Advisor asked Dr Iacovelli about the evidence and prospects for tailoring RCC immunotherapy.
Cancer Therapy Advisor (CTA): What are the current and emerging roles for immunotherapy in managing RCC?
Dr Iacovelli: Immunotherapy has improved the possibility of treating kidney cancer and increasing overall survival compared with the previous standard of care in patients who had received at least 1 therapy with sunitinib or pazopanib.
Ongoing studies are testing the possibility of improving survival in patients who have never received any therapy and in patients without metastases after nephrectomy as adjuvant therapy or in combination with other available drugs.
CTA: Are you optimistic, overall, about the prospects for personalizing RCC immunotherapy?
Dr Iacovelli: Personalized therapy will be the new paradigm for the coming years in treatment of solid tumors.
Great advances have been made for the treatment of lung, colon, and breast cancer but, unfortunately, the same results have not yet been reached in kidney cancer.
Regarding immunotherapy, non-conclusive results are available about the expression of PD-1/PD-L1. Its expression is not related to the efficacy of therapy; other well-known molecular factors such as BAP1 and PBRM1 are related to the prognosis, though they are not yet reliable markers for therapy.
CTA: You and your colleagues described the promise of combining vascular endothelial growth factor receptor (VEGFR)-targeted antiangiogenic therapy and immunotherapy. What is the evidence that blocking the VEGF signaling pathway can enhance immunotherapy’s antitumor effects?
Dr Iacovelli: Combination therapy is an exciting way to increase the efficacy of available therapies for the treatment of kidney cancer.
VEGFR is the main target of the antiangiogenic therapies (sunitinib and pazopanib), and [VEGFR] has been found on some immune cells where it is able to mediate activation or suppression of immune response.
The inhibition of VEGFR could enhance the immune system by increasing MHC-II expression, a protein responsible of the antigen presentation and, finally, of the activation of immune response against cancer.
Another connection between angiogenesis and the immune system has been investigated in a recent study reporting that tumors with VHL deletion have increased levels of PD-L1 related to HIF-2alpha expression, another protein involved in tumor progression.
Thus, patients with tumors harboring VHL deletion might have an increased possibility of responding to immunotherapy.