ArticleCancer immunology, immunotherapy : CII2020
Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets.
Article in Cancer immunology, immunotherapy : CII, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A systematic investigation of clear cell renal cell carcinoma using meta-analysis and systems biology approaches.Molecular genetics and genomics : MGG · 2024Pooled it
- Prognostic value of human leukocyte antigen G expression in solid tumors: a systematic review and meta-analysis.Frontiers in immunology · 2023Pooled it
- Is the HLA System Really Involved in Implantation, Pregnancy, or Abortion of the Fetus?: Strengths, Weaknesses, and Controversial Points.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- VISTA: bridging gaps in cancer immunotherapy.Discover oncology · 2026Review
- Immunosuppressive cell populations as potential drivers of extrinsic immune checkpoint inhibition resistance in clear cell renal cell carcinoma.Oncology reviews · 2026Review
- Prognostic impact of HLA-G expression in cervical squamous cell carcinoma: correlation with PD-L1 and CD8-positive tumor infiltrating lymphocytes.Frontiers in immunology · 2026Article
- Immune Landscape and Application of Immune Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2025Review
- VISTA: An Emerging Immune Checkpoint With Clinical Relevance Across Diverse Malignancies.Immune network · 2025Review
- Immune Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma (ccRCC).International journal of molecular sciences · 2025Review
- Inhibitory leukocyte immunoglobulin-like receptors, subfamily B (LILRBs) in human diseases: structure, roles, mechanisms, and clinical applications.Theranostics · 2025Review
- Article
- Harnessing the potential of HLA-G in cancer therapy: advances, challenges, and prospects.Journal of translational medicine · 2024Review
- Signaling lymphocytic activation molecule family receptors as potential immune therapeutic targets in solid tumors.Frontiers in immunology · 2024Review
- Emerging Immune Checkpoint Molecules on Cancer Cells: CD24 and CD200.International journal of molecular sciences · 2023Review
- Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice.Biomedicines · 2023Review
- Perspectives of targeting LILRB1 in innate and adaptive immune checkpoint therapy of cancer.Frontiers in immunology · 2023Review
- Identification and Validation of a Five-Gene Diagnostic Signature for Preeclampsia.Frontiers in genetics · 2022Article
- Elevated SNRPA1, as a Promising Predictor Reflecting Severe Clinical OutcomeFrontiers in immunology · 2022Article
- The Human Leukocyte Antigen G as an Immune Escape Mechanism and Novel Therapeutic Target in Urological Tumors.Frontiers in immunology · 2022Review
- Fibronectin enhances tumor metastasis through B7-H3 in clear cell renal cell carcinoma.FEBS open bio · 2021Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clear cell renal cell carcinoma (ccRCC) constitutes the most common renal cell carcinoma subtype and has long been recognized as an immunogenic cancer. As such, significant attention has been directed toward optimizing immune-checkpoints (IC)-based therapies. Despite proven benefits, a substantial number of patients remain unresponsive to treatment, suggesting that yet unreported, immunosuppressive mechanisms coexist within tumors and their microenvironment. Here, we comprehensively analyzed and ranked forty-four immune-checkpoints expressed in ccRCC on the basis of in-depth analysis of RNAseq data collected from the TCGA database and advanced statistical methods designed to obtain the group of checkpoints that best discriminates tumor from healthy tissues. Immunohistochemistry and flow cytometry confirmed and enlarged the bioinformatics results. In particular, by using the recursive feature elimination method, we show that HLA-G, B7H3, PDL-1 and ILT2 are the most relevant genes that characterize ccRCC. Notably, ILT2 expression was detected for the first time on tumor cells. The levels of other ligand-receptor pairs such as CD70:CD27; 4-1BB:4-1BBL; CD40:CD40L; CD86:CTLA4; MHC-II:Lag3; CD200:CD200R; CD244:CD48 were also found highly expressed in tumors compared to adjacent non-tumor tissues. Collectively, our approach provides a comprehensible classification of forty-four IC expressed in ccRCC, some of which were never reported before to be co-expressed in ccRCC. In addition, the algorithms used allowed identifying the most relevant group that best discriminates tumor from healthy tissues. The data can potentially assist on the choice of valuable immune-therapy targets which hold potential for the development of more effective anti-tumor treatments.
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