ArticleCancer science2019
Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- First-line pembrolizumab-axitinib versus sunitinib in metastatic RCC: subgroup analysis of patients enrolled in the phase 3 KEYNOTE-426 in Eastern Asia.Japanese journal of clinical oncology · 2025Trial
- Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study.International journal of clinical oncology · 2022Trial
- Prognostic value of PD-L1 in patients with metastatic renal cell carcinoma (mRCC) treated with antiangiogenic first line drugs (PROANG-SOGUG study).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Cytoplasmic Morphology Predicts the Tumor Immune Microenvironment and Recurrence in Localized Clear Cell Renal Cell Carcinoma.Annals of surgical oncology · 2026Article
- Multi-omics pan-cancer study of SPTBN2 and its value as a potential therapeutic target in pancreatic cancer.Scientific reports · 2024Article
- A potential immunotherapeutic and prognostic biomarker for multiple tumors including glioma: SHOX2.Hereditas · 2023Article
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- In situ vertical alignment of 2D MoSMikrochimica acta · 2022Article
- As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner.Cancer cell international · 2022Article
- A Pan-Cancer Analysis of the Oncogenic Role of Cell Division Cycle-Associated Protein 4 (CDCA4) in Human Tumors.Frontiers in immunology · 2022Article
- Application of Regulatory Cell Death in Cancer: Based on Targeted Therapy and Immunotherapy.Frontiers in immunology · 2022Review
- Pan-Cancer Analysis Shows That ALKBH5 Is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Gliomas.Frontiers in immunology · 2022Article
- The role and therapeutic significance of the anoikis pathway in renal clear cell carcinoma.Frontiers in oncology · 2022Article
- The potential value of cuprotosis (copper-induced cell death) in the therapy of clear cell renal cell carcinoma.American journal of cancer research · 2022Article
- Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer.International urology and nephrology · 2021Article
- Mechanisms of PD-L1 Regulation in Malignant and Virus-Infected Cells.International journal of molecular sciences · 2021Review
- Article
- Using Genomic and Transcriptome Analyses to Identify the Role of the Oxidative Stress Pathway in Renal Clear Cell Carcinoma and Its Potential Therapeutic Significance.Oxidative medicine and cellular longevity · 2021Article
- Tumor-Experienced Human NK Cells Express High Levels of PD-L1 and Inhibit CD8Frontiers in immunology · 2021Article
- Exploration of a Novel Prognostic Risk Signature and Its Effect on the Immune Response in Nasopharyngeal Carcinoma.Frontiers in oncology · 2021Article
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Authors and funding
13 authors at 9 institutions in 1 country.
Funding
Abstract
Recently, immunotherapy based on blocking immune checkpoints with programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) Abs has been introduced for the treatment of advanced clear cell renal cell carcinoma (ccRCC), especially tumors resistant to vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs), but the significance of their expression in the tumor microenvironment is unclear. We investigated these immune checkpoint markers in tumor cells and tumor-infiltrating immune cells (TIIC) in the tumor microenvironment of 100 untreated and 25 VEGF-TKI-treated primary ccRCC tissues. Upregulated expression of PD-1 and PD-L1 by TIIC, and PD-L1 by tumor cells was associated with the histological grade and unfavorable prognosis of RCC patients. High PD-1 and PD-L1 expression by TIIC was associated with a poorer response to VEGF-TKI, whereas PD-L1 expression by tumor cells did not affect the efficacy of the treatment. Furthermore, increased PD-1-positive TIIC and PD-L1-positive TIIC were observed in tumors treated with VEGF-TKIs compared with those in untreated tumors. Our data suggest that PD-1 and PD-L1 expression by TIIC in the tumor microenvironment is involved in treatment resistance, and that sequential therapy with immune checkpoint inhibitors could be a promising therapeutic strategy for ccRCC resistant to VEGF-TKI treatment.
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