Novel 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.
Scientific reports. 2024 Jan 17*** epublish ***
Nirmish Singla, Thomas R Nirschl, Aleksandar Z Obradovic, Eugene Shenderov, Kara Lombardo, Xiaopu Liu, Alice Pons, Jelani C Zarif, Steven P Rowe, Bruce J Trock, Hans J Hammers, Trinity J Bivalacqua, Phillip M Pierorazio, Julie S Deutsch, Tamara L Lotan, Janis M Taube, Yasser M A Ged, Michael A Gorin, Mohamad E Allaf, Charles G Drake
Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD, 21287, USA. ., Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA., Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA., Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD, 21287, USA., The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA., Division of Urology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Milton and Carroll Petrie Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Immuno-Oncology, The Janssen Pharmaceutical Companies of Johnson & Johnson, Raritan, NJ, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/38228729