KEY TAKEAWAYS
- The phase 1 study investigated the impact of PD-1 inhibitors on immune cells in the tumor and the bloodstream.
- The study’s results supported the use of ICIs like nivolumab before surgery in severe ccRCC cases.
New approaches during surgery are required to lower the chances of disease recurrence in patients being treated for high-risk, non-spreading clear cell renal cell carcinoma (ccRCC). This study aimed to (1) understand how PD-1 blocking affects primary tumor-infiltrating and circulating immune cell populations in ccRCC and (2) link the tumor microenvironment and circulating immune cell compositions with the effectiveness of anti-PD-1 treatments.
The phase 1 study used nivolumab before nephrectomy in 15 patients with non-metastatic ccRCC. Researchers used tissues from these patients to determine how PD-1 blocking impacts immune cells in ccRCC and to find connections between the changing immune environment and response to anti-PD-1, utilizing techniques like fluorescence-activated cell sorting, bulk RNA sequencing with protein activity deduction, and enzyme-linked immunosorbent assay for circulating cytokines.
The trial showed that nivolumab triggers an inflammation-promoting condition in the primary tumor, demonstrated by a consistent rise in the aggressive T cell phenotype and a drop in controlling T cell groups. The baseline immune cell presence in the primary tumor, specifically the aggressive T cells and myeloid cells, combined with a reduction in angiogenesis, is linked to a positive response to nivolumab. Nivolumab leads to a boost in CTLA-4 in the primary tumor, and following nephrectomy, there’s a rise in levels of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB in the blood.
The results formed the basis for considering neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor is still present. This gives a basis for introducing new ICI combinations during the surgery process.
Source: https://www.auajournals.org/doi/10.1097/JU.0000000000003353.05
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02575222
Singla, Nirmish; Nirschl, Thomas; Obradovic, Aleksandar; Shenderov, Eugene; Lombardo, Kara; Liu, Xiaopu; Pons, Alice; Zarif, Jelani; Rowe, Steven; Trock, Bruce; Hammers, Hans; Bivalacqua, Trinity; Pierorazio, Phillip; Deutsch, Julie; Lotan, Tamara; Taube, Janis; Ged, Yasser; Gorin, Michael; Allaf, Mohamad; Drake, Charles PD43-05 IMMUNOMODULATORY RESPONSE TO NEOADJUVANT NIVOLUMAB IN NON-METASTATIC CLEAR CELL RENAL CELL CARCINOMA: RESULTS FROM a PHASE I TRIAL, Journal of Urology: April 2023 – Volume 209 – Issue Supplement 4 doi: 10.1097/JU.0000000000003353.05
