ArticleJournal for immunotherapy of cancer2020
HHLA2 and PD-L1 co-expression predicts poor prognosis in patients with clear cell renal cell carcinoma.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers, 2 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Prognostic Value of HHLA2 in Patients with Solid Tumors: A Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Prognostic value of HHLA2 expression in solid tumors: A meta-analysis based on the Chinese population.Medicine · 2021Pooled it
- Clinical Evaluation of HHLA2 in Hormone Receptor-Positive Breast Cancer: Expression Patterns and Prognostic Implications.Biomedicines · 2026Article
- Immune checkpoint profiling of B7-H proteins predicts survival and treatment response in metastatic clear cell renal cell carcinoma.The journal of pathology. Clinical research · 2026Article
- Cancer Cell-Intrinsic Cholesterol Induces Lipid-Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neutrophil extracellular traps and metabolic reprogramming in renal cell carcinoma: implications for tumor progression and immune-based therapeutics.Cancer biology & medicine · 2025Review
- Targeting HVEM-GPT2 axis: a novel approach to T cell activation and metabolic reprogramming in non-small cell lung cancer therapy.Cancer immunology, immunotherapy : CII · 2025Article
- Distinct Roles of HHLA2 and PD-L1 in the Immune Cell and Prognosis of Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2025Article
- Identification of kidney renal clear cell carcinoma prognosis based on gene expression and clinical information.Frontiers in molecular biosciences · 2025Article
- Construction of a risk model associated with tryptophan metabolism and identification of related molecular subtypes in laryngeal squamous cell carcinoma.Frontiers in genetics · 2025Article
- Impact of B7-H3 expression on metastasis, immune exhaustion and JAK/STAT and PI3K/AKT pathways in clear cell renal cell carcinoma.Oncoimmunology · 2024Article
- PD1/PD-L1 blockade in clear cell renal cell carcinoma: mechanistic insights, clinical efficacy, and future perspectives.Molecular cancer · 2024Review
- Increased coexpression of PD-L1 and IDO1 is associated with poor overall survival in patients with NK/T-cell lymphoma.Leukemia · 2024Article
- Identification of a risk model for prognostic and therapeutic prediction in renal cell carcinoma based on infiltrating M0 cells.Scientific reports · 2024Article
- Diagnostic, predictive and prognostic molecular biomarkers in clear cell renal cell carcinoma: A retrospective study.Cancer reports (Hoboken, N.J.) · 2024Review
- Review
- Article
- Review
- Clinical Significance of HHLA2 as a Novel Therapeutic Target for Colorectal Cancer.Current cancer drug targets · 2024Article
- Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma.iScience · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection:2020
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough clear cell renal cell carcinoma (ccRCC) is well known as a highly immunogenic tumor, only a small subset of patients could benefit from current immunotherapy, which might be due to the heterogeneity of immune microenvironment in ccRCC. So, it is meaningful to explore novel immunotherapy or combination therapy for improving therapeutic efficacy. HHLA2, a newly discovered B7 family member, is prevalently expressed in numerous tumors, including ccRCC. This study aimed to investigate the prognostic impact of HHLA2/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs).
methodsThe expression levels of HHLA2, PD-L1, CD8, and CD4 in cancer tissues from cases (206 in the training cohort and 197 in the validation cohort) with surgically resectable primary ccRCC were evaluated by immunohistochemistry.
resultsThe positive rates of HHLA2 were much higher than those of PD-L1 in ccRCC tissues. HHLA2-positive expression was significantly associated with necrosis, microvascular invasion, advanced Fuhrman nuclear, and TNM stage and indicated a shorter progression-free survival (PFS) and overall survival (OS) in both cohorts. Moreover, patients with HHLA2/PD-L1 co-expression suffered the highest risk of disease progression and death by a significant margin. Besides, HHLA2/PD-L1 co-expression was significantly associated with a high density of CD8
conclusionsThe expression of HHLA2 is more frequent than PD-L1 in ccRCC. HHLA2/PD-L1 co-expression had an adverse impact on the prognoses of patients with ccRCC; this finding provides a rationale for combination immunotherapy with anti-HHLA2 and PD-L1 blockage for patients with ccRCC in the future.
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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.