ArticleESMO open2026
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.
Article in ESMO open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundImmune checkpoint inhibition with ipilimumab and nivolumab prolongs survival in renal cell carcinoma (RCC). Tumors with sarcomatoid and/or rhabdoid features are considered responsive to immune checkpoint inhibitors (ICIs), despite their aggressive nature. Although sarcomatoid/rhabdoid dedifferentiation is not considered a distinct subtype of RCC, these tumors differ clinically and molecularly from nonsarcomatoid/rhabdoid RCC tumors. We sought to identify biomarkers underlying responsiveness to ICIs and compare the immune microenvironments of tumors with or without sarcomatoid/rhabdoid components. PATIENTS AND
methodsWe constructed a tissue microarray from archived RCC tumors collected from patients treated with first-line ipilimumab and nivolumab. Digital spatial profiling was carried out using NanoString's GeoMx platform with a panel of 58 proteins. Regions of interest were segmented into immune [cluster of differentiation (CD)68+ and CD45+] and tumor [positive for both cytokeratin and carbonic anhydrase 9 (CAIX+ CK+)] compartments. To investigate marker expression in tumors with and without sarcomatoid/rhabdoid dedifferentiation, two additional tissue microarrays were analyzed, comprising cohorts of patients treated with heterogeneous first-line therapies. Key findings were validated by immunohistochemistry.
resultsAfter quality control, 44 pretreatment tumors from 44 patients were analyzed. Tumor programmed death-ligand 1 (PD-L1) expression was higher in responders (P = 0.03) and associated with improved progression-free survival [PFS; hazard ratio (HR) 0.4, 95% confidence interval (CI) 0.2-0.8, P = 0.01] and overall survival (OS; HR 0.2, 95% CI 0.06-0.5, P < 0.005) on multivariable analysis. This finding was confirmed by immunohistochemistry. In the CD45+ compartment of sarcomatoid/rhabdoid tumors, CD25 expression was associated with worse PFS (HR 58.8, 95% CI 2.8-1250, P = 0.01). Differential expression analysis showed higher CD66b in sarcomatoid/rhabdoid tumors (log
conclusionsTumor PD-L1 is associated with better PFS and OS after ipilimumab + nivolumab. In the sarcomatoid/rhabdoid subset, lower CD25 (a marker of regulatory T cells) was associated with improved PFS, while increased neutrophil infiltration (CD66b+/MPO+) emerged as a novel feature of sarcomatoid/rhabdoid tumors, which may be harnessed for therapeutic benefit in this population.
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