Association of myeloid-derived suppressor cell (MDSC) dynamics with clinical response to nivolumab in metastatic clear cell renal carcinoma patients (mRCC): Results from the I-RENE Meet-URO 8 study.

• DOI: 10.1200/jco.2025.43.5_suppl.586
• Publication Date: 2025-02-18T14:33:57Z
• Authors: Elena Verzoni; Monica Rodolfo; Viviana Vallacchi; Katia Todoerti; Paolo Andrea Zucali; Bruno Perrucci; Sebastiano Buti; Marco Maruzzo; Isabella Vittimberga; Giuseppe Fornarini; Eleonora Gusmaroli; Agata Cova; Simona Frigerio; Francesca Rini; Paola Squarcina; Luca Lalli; Giuseppe Procopio; Licia Rivoltini; Veronica Huber
• Keywords: Myeloid-derived Suppressor Cell

586 Background: Immune checkpoint blockade is a standard-of-care treatment for mRCC patients, but the immune mechanisms driving clinical benefit remain underexplored. In I-RENE trial (NCT04891055), we conducted comprehensive evaluation of myeloid-derived suppressor cell (MDSC) and lymphoid dynamics their impact on efficacy nivolumab. Methods: The study prospective, translational, real-world multicenter involving patients treated with nivolumab after failure previous VEGFR-targeted therapies. Sixty were enrolled between December 2018 August 2022. Peripheral blood (PB) samples collected at baseline 2, 4, 12 weeks, as well disease progression. PBMCs analyzed by high-resolution flow cytometry (profiling 144 myeloid subsets), plasma was assessed using multiplex analysis (69 soluble factors). CD14+ monocytes from PB tumor tissue subjected to RNA sequencing. Results: Significant modulations in detectable early 2 weeks into across all regardless response, persisted throughout 3-month observation period. These changes included substantial alterations profiles cells factors. Responders exhibited marked reduction monocyte subsets associated suppression, such CD14+HLA-DR- cells, CD14+PD-L1+ intermediate monocytes. contrast, non-responders showed progressive increase suppressive concomitant decrease involved anti-tumor immunity, including non-classical expressing HLA-DR CX3CR1. Lymphoid compartment revealed that responders experienced an CD8+ T CD4+ effector memory along CD38+ cells. Conversely, significant upregulation senescent (KLRG1+CD28-CD57+) All progressing notable resurgence (HLA-DR-, PD-L1+), confirmed enriched MDSC gene signature, Notably, detrimental role myeloid-driven suppression further signature matched samples. Conclusions: pervasive committed evident even before radiological progression persists despite immunotherapy. findings highlight need identification immune-suppressive infiltrates development strategies overcome or reprogram these both systemic level, following diagnosis.