ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2025
Tumor-Intrinsic and Microenvironmental Determinants of Impaired Antitumor Immunity in Chromophobe Renal Cell Carcinoma.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Advancing clinical trials for rare renal cell carcinoma subtypes: Consensus statements from the International Kidney Cancer Symposium North America 2025 think tank.Urologic oncology · 2026Article
- Reviving cancer vaccines in renal cell carcinoma: a new chapter in immunotherapy for kidney cancer.Immuno-oncology technology · 2026Review
- mTORC1 activation induces B7-H3-dependent metabolic reprogramming in renal cell carcinoma (RCC).Oncogene · 2026Article
- Evaluating the clinical significance of tumor-expressed C-reactive protein in chromophobe renal cell carcinoma.Scientific reports · 2026Article
- Chromophobe renal cell carcinoma with nodal involvement: A rare case report highlighting unusual molecular features.Urology case reports · 2026Article
- The seventh kidney cancer research summit: progress in accelerating cures.The oncologist · 2026Article
- Perioperative Immune-Checkpoint Inhibition in Renal Cell Carcinoma: Lessons Learned and Future Directions.Cancers · 2026Review
- Serum ferritin change rate combined with a multidimensional inflammation model for predicting efficacy and survival in extensive-stage small-cell lung cancer patients undergoing immunotherapy: a single-center, retrospective cohort study.Frontiers in immunology · 2026Article
- Developing of potential mRNA vaccines based on tumor antigens and immune subtypes of esophageal cancer.Translational cancer research · 2025Article
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Authors and funding
48 authors.
Funding
Abstract
purposeWhile immune checkpoint inhibition (ICI) has transformed the management of many advanced renal cell carcinomas (RCCs), the determinants of effective antitumor immunity for chromophobe RCC (ChRCC) and renal oncocytic tumors remain an unmet clinical and scientific need.
methodsSingle-cell transcriptomic and T-cell receptor profiling was performed on tumor and adjacent normal tissue of patients with ChRCC and renal oncocytic neoplasms. Using machine learning, the cellular origin of renal oncocytic neoplasms was evaluated, with analysis of associated oncogenic pathways. Using immunohistochemistry, immune infiltration was analyzed in renal oncocytic neoplasms in comparison with clear cell RCC (ccRCC). Immune checkpoint expression, clonal expansion, and tumor specificity were compared between ChRCC and ccRCC. Using the International Metastatic RCC Database Consortium data set, clinical outcomes of patients with metastatic ChRCC (mChRCC) treated with first-line systemic regimens were compared with those of patients with ccRCC.
resultsWe validated α-intercalated cells as the cellular origin of renal oncocytic neoplasms. We identified a downregulation of HLA class I molecules with enrichment of potentially targetable pathways including mammalian target of rapamycin and ferroptosis in ChRCC. The tumor microenvironment of ChRCC showed markedly decreased immune infiltration, with a pronounced depletion in tumor-infiltrating CD8
conclusionImmunogenomic analysis of ChRCC revealed profound depletion of T cells, with an immune phenotype marked by a lack of expression of immune checkpoints and poor tumor specificity, suggesting that the few T cells in these tumor types are likely nonspecific bystanders. This immune-cold environment hinders an effective response to immunotherapy and underscores the need for ChRCC-tailored treatments designed to improve tumor-specific T-cell infiltration into the microenvironment.
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