Association between PD-1 expression on tumor-infiltrating regulatory T cells and resistance to first-line nivolumab in advanced clear cell renal cell carcinoma: Insights from the HCRN GU16-260 clinical trial.

• DOI: 10.1200/jco.2025.43.5_suppl.590
• Publication Date: 2025-02-18T14:38:27Z
• Authors: Razan Mohanna; Berkay Simsek; Nourhan El Ahmar; Opeyemi Jegede; Sayed Matar; Morgan Paul; Yasmin Nabil Laimon; Gabriel Roberti D...; Andrew Delcea; Toni K. Choueiri; David A. Braun; Naomi Balzer Haas; Hans J. Hammers; Mehmet Asim Bilen; Mark N. Stein; Jeffrey A. Sosman; Catherine J. Wu; David F. McDermott; Michael B. Atkins; Sabina Signoretti
• Keywords: Acquired resistance; Second line

590 Background: Inhibition of PD-1 signaling in regulatory T cells (Tregs) has been shown to enhance their immunosuppressive function. We previously demonstrated that high levels expression on tumor-infiltrating Tregs are associated with resistance nivolumab (nivo) monotherapy pretreated patients advanced clear cell renal carcinoma (ccRCC) from the CheckMate-025 trial (Denize et al, 2024). Here, we aim validate these findings first-line setting. Methods: Primary tumor tissues ccRCC (n=70) treated nivo HCRN GU16-260 clinical were analyzed using multiparametric immunofluorescence (IF). The percentage PD-1+ was quantified by image analysis. Associations objective response rate (ORR) and progression-free survival (PFS) evaluated logistic Cox regression models, along Fisher’s exact test log-rank for statistical inference, as appropriate. alpha level set at 5% (one-sided). Results: In line our previous findings, Tregs, measured a continuous variable, did not have statistically significant association PFS [HR = 2.62; p 0.169] or ORR [OR 0.72; 0.42]. Using an optimized cut-off based minimal p-value ORR, (≥36%) (8/70) experienced shorter median (3.4 vs. 10.9 months; 0.001) trend toward lower (12.5% 43.6%; 0.093) compared those low (62/70). Conclusions: is worse outcomes therapy ccRCC, confirming findings. These results highlight therapeutic potential targeting overcome improve efficacy blockade, which currently being (HCRN GU22-587).