ArticleJournal for immunotherapy of cancer2019
Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 3 of them syntheses that pooled it.
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Who cites it
96 citing papers in PubMed, 3 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- Pooled it
- Prognostic Role of Soluble Programmed Death Ligand 1 in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- TIM-3 as a Prognostic Marker and a Potential Immunotherapy Target in Human Malignant Tumors: A Meta-Analysis and Bioinformatics Validation.Frontiers in oncology · 2021Pooled it
- Soluble B7-H6 as a Novel Diagnostic Biomarker for Post-Hepatitis B Cirrhosis: A Clinical Value Study.Journal of clinical laboratory analysis · 2026Article
- Soluble Immune Checkpoints as Prognostic Biomarkers in Small Cell Lung Cancer Patients Treated with Chemotherapy and Anti-PD-L1.International journal of molecular sciences · 2026Article
- Cytokines and immunologic checkpoint molecules in predicting success of allergen immunotherapy.Scientific reports · 2026Article
- Association between B and T lymphocyte attenuator/herpes virus entry mediator immunoregulatory axis and outcome prediction in a mixed critically ill population.Scientific reports · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Soluble immune checkpoint proteins as predictive biomarkers for lymph node metastases in penile cancer.Frontiers in immunology · 2026Article
- A novel cuproptosis-related prognostic gene signature and validation of differential expression in colon cancer.Discover oncology · 2025Article
- Elevated Levels of sLAG-3 as a Possible Biomarker in Graves' Disease With and Without Thyroid Eye Disease: A Prospective Observational Case-Control Study.Medicina (Kaunas, Lithuania) · 2025Observational
- Liquid biopsy using plasma proteomics in predicting efficacy and tolerance of PD-1/PD-L1 blockades in NSCLC: a prospective exploratory study.Molecular biomedicine · 2025Article
- Serum soluble Tim‑3 is elevated in patients with cervical cancer and is higher in advanced clinical stages.Biomedical reports · 2025Article
- Soluble TIM-3, likely produced by myeloid cells, predicts resistance to immune checkpoint inhibitors in metastatic clear cell renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Soluble immune checkpoint factors reveal high-risk osteosarcoma subtypes and enable early metastasis prediction.Frontiers in immunology · 2025Article
- Sensitivity of renal cell carcinoma to cuproptosis: a bioinformatics analysis and experimental verification.Journal of Cancer · 2025Article
- GGTLC1 Is a Prognostic Biomarker in Renal Clear Cell Carcinoma.International journal of genomics · 2025Article
- The prognostic and predictive value of peripheral immune-related proteins in patients with lung cancer treated with radiotherapy.Frontiers in oncology · 2025Review
- The T cell-mediated tumor killing patterns revealed tumor heterogeneous and proposed treatment recommendation in ovary cancer.Discover oncology · 2024Article
- Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.International journal of molecular sciences · 2024Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundImmune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. With the exception of a few candidate biomarkers, the prognostic role of soluble immune checkpoint-related proteins in clear cell renal cell cancer (ccRCC) patients is largely uninvestigated.
methodsWe profiled the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, CD137, CD27 and CTLA-4) and their associations with the risk of recurrence and death in 182 ccRCC patients using a multiplex Luminex assay. Gene expression in tumors from a subset of participating patients (n = 47) and another 533 primary ccRCC from TCGA were analyzed to elucidate potential mechanisms. Our primary endpoint is overall survival; secondary endpoint is recurrence-free survival. Multivariate Cox proportional hazard model, unconditional logistic regression model, and Kaplan-Meier analysis were applied in the study.
resultssTIM3 and sLAG3 were significantly associated with advanced (stage III) disease (P < 0.05). sPD-L2 was the strongest predictor of recurrence (HR 2.51, 95%CI 1.46-4.34, P = 9.33E-04), whereas high sBTLA and sTIM3 was associated with decreased survival (HR 6.02, 95%CI 2.0-18.1, P = 1.39E-03 and HR 3.12, 95%CI 1.44-6.75, P = 3.94E-03, respectively). Risk scores based on sTIM3 and sBTLA indicated that the soluble immune checkpoint-related proteins jointly predicted recurrence and death risks of ccRCC (P = 0.01 and 4.44E-04, respectively). Moreover, sLAG3 and sCD28 were found negatively correlated with cytolytic activity of T cells in tumors (rho = -0.31 and - 0.33, respectively).
conclusionsOur study provides evidence that soluble immune checkpoint-related proteins may associate with advanced disease, recurrence and survival in ccRCC patients, which highlights the prognostic values of soluble immune checkpoint-related proteins. Future independent validation in prospective studies is warranted.
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