Author:
Singla Nirmish,Nirschl Thomas R.,Obradovic Aleksandar Z.,Shenderov Eugene,Lombardo Kara,Liu Xiaopu,Pons Alice,Zarif Jelani C.,Rowe Steven P.,Trock Bruce J.,Hammers Hans J.,Bivalacqua Trinity J.,Pierorazio Phillip M.,Deutsch Julie S.,Lotan Tamara L.,Taube Janis M.,Ged Yasser M. A.,Gorin Michael A.,Allaf Mohamad E.,Drake Charles G.
Abstract
AbstractNovel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.
Publisher
Springer Science and Business Media LLC