PD-L1 and Neutrophils Predict RCC Outcomes with Immunotherapy
Publication Title: Compartment-specific immune and tumor markers associated with clinical outcomes in patients with and without sarcomatoid/rhabdoid renal cell carcinoma treated with ipilimumab and nivolumab.
Summary
- Question
- This study investigated molecular biomarkers associated with clinical outcomes in patients with renal cell carcinoma (RCC) treated with the immune checkpoint inhibitors ipilimumab and nivolumab. Specifically, the researchers examined differences in biomarkers between tumors with and without sarcomatoid/rhabdoid features, which are aggressive dedifferentiated tumor subtypes known to respond well to these therapies.
- Why it Matters
- Understanding the molecular factors that influence treatment response is critical for improving patient outcomes in RCC, particularly for aggressive subtypes like sarcomatoid/rhabdoid tumors. Identifying biomarkers could enable personalized treatment strategies, optimize therapeutic choices, and guide future drug development. This research is relevant to oncologists, researchers, and patients seeking more effective interventions for metastatic RCC.
- Methods
- The researchers analyzed archived tumor samples from 44 patients with RCC who received ipilimumab and nivolumab as first-line therapy. Using NanoString’s GeoMx platform, they profiled 58 proteins in distinct tissue compartments, including immune cells and tumor cells. Key findings were validated through immunohistochemistry (IHC), which involves staining tissue samples to identify specific proteins.
- Key Findings
- Higher expression of programmed death-ligand 1 (PD-L1), a protein that suppresses immune responses, in tumor cells was linked to improved progression-free survival (PFS) and overall survival (OS). In sarcomatoid/rhabdoid tumors, elevated levels of CD25, a marker of regulatory T cells (immune cells that inhibit immune responses), were associated with worse PFS. Additionally, these tumors showed increased neutrophil infiltration, indicated by higher levels of CD66b and myeloperoxidase (MPO), which are neutrophil-specific markers.
- Implications
- The findings highlight PD-L1 as a potential predictive biomarker for selecting RCC patients likely to benefit from ipilimumab and nivolumab therapy. The association of CD25 with poor outcomes in sarcomatoid/rhabdoid tumors suggests that targeting regulatory T cells may improve responses in this aggressive subtype. Neutrophil infiltration could also play a role in the unique immune microenvironment of these tumors, presenting another potential therapeutic avenue.
- Next Steps
- Future research should validate these biomarkers in larger, diverse cohorts and investigate their predictive value in randomized trials. Additional studies are needed to explore the role of neutrophils in sarcomatoid/rhabdoid tumors and their potential as therapeutic targets. Integrating tissue-based biomarkers with circulating markers could enhance precision medicine approaches in RCC.
- Funding Information
- This research was supported in part by the National Institutes of Health (award 5R01CA269349). Additional funding was provided by the Department of Defense (award KC230193) and the NIH Yale Cancer Center Advanced Training Program (award T32 CA233414).
Full Citation
Savion-Gaiger N, Perales O, Su DG, Bar-Ziv D, Challa P, Djureinovic D, Yi I, Adeniran A, Kluger H, Schoenfeld D. Compartment-specific immune and tumor markers associated with clinical outcomes in patients with and without sarcomatoid/rhabdoid renal cell carcinoma treated with ipilimumab and nivolumab. ESMO Open 2026, 11: 106908. PMID: 42013628, DOI: 10.1016/j.esmoop.2026.106908.