ArticleGenome medicine2022
Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02595918 (A Pilot Study of Preoperative Nivolumab in High-Risk Non-Metastatic and Metastatic Renal Cell Carcinoma), which is not on this map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
A Pilot Study of Preoperative Nivolumab in High-Risk Non-Metastatic and Metastatic Renal Cell Carcinoma
Who cites it
37 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma.Cancer cell · 2026Article
- Chimeric Antigen Receptor-Immune Cell-Based Therapies for Clear Cell Renal Cell Carcinoma: Latest Advancements and Directions.Cancers · 2026Review
- Concurrent tissue and circulating tumor DNA analysis in renal cell carcinoma: insights from a multimodal database.The oncologist · 2026Article
- Clinical value and mechanism of CDKN2A in clear cell renal cell carcinoma.Discover oncology · 2025Article
- Immunological features of clear-cell renal-cell carcinoma and resistance to immune checkpoint inhibitors.Nature reviews. Nephrology · 2025Review
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
- Comparison of Histologic Parameters and Predictive Gene Signatures in Clear Cell Renal Cell Carcinoma Response to Systemic Therapy.Pathology international · 2025Article
- High intratumoral heterogeneity in clear cell renal cell carcinoma is associated with reduced immune response and survival.Translational andrology and urology · 2025Article
- Integrating machine learning and multi-omics analysis to unveil key programmed cell death patterns and immunotherapy targets in kidney renal clear cell carcinoma.Scientific reports · 2025Article
- Potential of Metabolic MRI to Address Unmet Clinical Needs in Localised Kidney Cancer.Cancers · 2025Review
- Integrative Analysis of Immune- and Metabolism-Related Genes Identifies Robust Prognostic Signature and PYCR1 as a Carcinogenic Regulator in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2025Article
- Review
- Review
- Histopathology based AI model predicts anti-angiogenic therapy response in renal cancer clinical trial.Nature communications · 2025Article
- Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.Cancer discovery · 2025Article
- Effects of Vitamin D on tumor cell proliferation and migration, tumor initiation and anti-tumor immune response in head and neck squamous cell carcinomas.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.Nature communications · 2024Article
Corrections and comments
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Authors and funding
29 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntratumoral heterogeneity (ITH) is a hallmark of clear cell renal cell carcinoma (ccRCC) that reflects the trajectory of evolution and influences clinical prognosis. Here, we seek to elucidate how ITH and tumor evolution during immune checkpoint inhibitor (ICI) treatment can lead to therapy resistance.
methodsHere, we completed a single-arm pilot study to examine the safety and feasibility of neoadjuvant nivolumab in patients with localized RCC. Primary endpoints were safety and feasibility of neoadjuvant nivolumab. Then, we spatiotemporally profiled the genomic and immunophenotypic characteristics of 29 ccRCC patients, including pre- and post-therapy samples from 17 ICI-treated patients. Deep multi-regional whole-exome and transcriptome sequencing were performed on 29 patients at different time points before and after ICI therapy. T cell repertoire was also monitored from tissue and peripheral blood collected from a subset of patients to study T cell clonal expansion during ICI therapy.
resultsAngiogenesis, lymphocytic infiltration, and myeloid infiltration varied significantly across regions of the same patient, potentially confounding their utility as biomarkers of ICI response. Elevated ITH associated with a constellation of both genomic features (HLA LOH, CDKN2A/B loss) and microenvironmental features, including elevated myeloid expression, reduced peripheral T cell receptor (TCR) diversity, and putative neoantigen depletion. Hypothesizing that ITH may itself play a role in shaping ICI response, we derived a transcriptomic signature associated with neoantigen depletion that strongly associated with response to ICI and targeted therapy treatment in several independent clinical trial cohorts.
conclusionsThese results argue that genetic and immune heterogeneity jointly co-evolve and influence response to ICI in ccRCC. Our findings have implications for future biomarker development for ICI response across ccRCC and other solid tumors and highlight important features of tumor evolution under ICI treatment.
trial registrationThe study was registered on ClinicalTrial.gov (NCT02595918) on November 4, 2015.
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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.