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.
[BACKGROUND] Immune checkpoint inhibition with ipilimumab and nivolumab prolongs survival in renal cell carcinoma (RCC).
- p-value P = 0.03
- p-value P = 0.01
- 95% CI 0.06-0.5
APA
Savion-Gaiger N, Perales O, et al. (2026). 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, 11(5), 106908. https://doi.org/10.1016/j.esmoop.2026.106908
MLA
Savion-Gaiger N, et al.. "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, vol. 11, no. 5, 2026, pp. 106908.
PMID
42013628
Abstract
[BACKGROUND] Immune 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 METHODS] We 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.
[RESULTS] After 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 fold change = 2.2, P < 0.001), validated by immunohistochemistry with significantly higher myeloperoxidase (MPO) staining (χ = 15.7, df = 3, P < 0.001).
[CONCLUSIONS] Tumor 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.
[PATIENTS AND METHODS] We 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.
[RESULTS] After 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 fold change = 2.2, P < 0.001), validated by immunohistochemistry with significantly higher myeloperoxidase (MPO) staining (χ = 15.7, df = 3, P < 0.001).
[CONCLUSIONS] Tumor 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.