Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2022
Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Molecular biomarkers in metastatic clear cell renal cell carcinoma treated with first-line immune combinations: a systematic review of phase III randomized clinical trials by Meet-URO group.Cancer metastasis reviews · 2026Pooled it
- From Genes to Proteins: The Indispensable Role of Proteogenomics in Advancing Clear Cell Renal Cell Carcinoma Research.International journal of molecular sciences · 2026Review
- Article
- Prognostic and Predictive Value of the Clearseq1-4 Tumor Microenvironment Classification in Localized and Metastatic Clear-Cell Renal Cell Carcinoma.Cancer research communications · 2026Article
- Investigating the determinants of immunotherapy response in the primary tumour of clear cell renal cell carcinoma (RCC).BMJ oncology · 2026Article
- Pre-treatment C-reactive protein level is a prognostic marker of patients treated with immune checkpoint inhibitors for renal cell carcinoma: a systematic review and meta-analysis.Translational andrology and urology · 2025Article
- Validation of a 15-Gene Prognostic Signature in Metastatic Clear Cell Renal Cell Carcinoma.JCO precision oncology · 2025Article
- Overview on biomarkers for immune oncology drugs.Exploration of targeted anti-tumor therapy · 2025Review
- Community assessment of methods to deconvolve cellular composition from bulk gene expression.Nature communications · 2024Article
- Effectiveness of switch therapy from tyrosine kinase inhibitors to immune checkpoint inhibitors: the need for biomarkers to establish treatment strategies in patients with metastatic renal cell carcinoma.Translational andrology and urology · 2024Article
- Dual-loss of PBRM1 and RAD51 identifies hyper-sensitive subset patients to immunotherapy in clear cell renal cell carcinoma.Cancer immunology, immunotherapy : CII · 2024Article
- PD-L1 as a Urine Biomarker in Renal Cell Carcinoma-A Case Series and Proof-of-Concept Study.Diagnostics (Basel, Switzerland) · 2024Article
- NKG2AJournal for immunotherapy of cancer · 2024Article
- A murine model to evaluate immunotherapy effectiveness for human Fanconi anemia-mutated acute myeloid leukemia.PloS one · 2024Article
- Article
- The Role of the Pathologist in Renal Cell Carcinoma Management.Hematology/oncology clinics of North America · 2023Review
- Predicting response and toxicity to immune checkpoint inhibitors in lung cancer using antibodies to frameshift neoantigens.Journal of translational medicine · 2023Article
- POLD1 as a Prognostic Biomarker Correlated with Cell Proliferation and Immune Infiltration in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2023Article
- Identification of berberine as a potential therapeutic strategy for kidney clear cell carcinoma and COVID-19 based on analysis of large-scale datasets.Frontiers in immunology · 2023Article
- Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity.Exploration of targeted anti-tumor therapy · 2023Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
purposePD-L1 expression on tumor cells (TC) is associated with response to anti-PD-1-based therapies in some tumor types, but its significance in clear cell renal cell carcinoma (ccRCC) is uncertain. We leveraged tumor heterogeneity to identify molecular correlates of TC PD-L1 expression in ccRCC and assessed their role in predicting response to anti-PD-1 monotherapy. EXPERIMENTAL
designRNA sequencing was performed on paired TC PD-L1 positive and negative areas isolated from eight ccRCC tumors and transcriptomic features associated with PD-L1 status were identified. A cohort of 232 patients with metastatic ccRCC from the randomized CheckMate-025 (CM-025) trial was used to confirm the findings and correlate transcriptomic profiles with clinical outcomes.
resultsIn both the paired samples and the CM-025 cohort, TC PD-L1 expression was associated with combined overexpression of immune- and cell proliferation-related pathways, upregulation of T-cell activation signatures, and increased tumor-infiltrating immune cells. In the CM-025 cohort, TC PD-L1 expression was not associated with clinical outcomes. A molecular RCC subtype characterized by combined overexpression of immune- and cell proliferation-related pathways (previously defined by unsupervised clustering of transcriptomic data) was enriched in TC PD-L1 positive tumors and displayed longer progression-free survival (HR, 0.32; 95% confidence interval, 0.13-0.83) and higher objective response rate (30% vs. 0%, P = 0.04) on nivolumab compared with everolimus.
conclusionsBoth TC-extrinsic (immune-related) and TC-intrinsic (cell proliferation-related) mechanisms are likely intertwined in the regulation of TC PD-L1 expression in ccRCC. The quantitation of these transcriptional programs may better predict benefit from anti-PD-1-based therapy compared with TC PD-L1 expression alone in ccRCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.