ArticlePloS one2012
Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
112 citing papers in PubMed, 176 citations in OpenAlex.
- Targeting Carcinoembryonic Antigen with DNA Vaccination: On-Target Adverse Events Link with Immunologic and Clinical Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- PD-1 identifies the patient-specific CD8⁺ tumor-reactive repertoire infiltrating human tumors.The Journal of clinical investigation · 2014Trial
- Molecular and immune correlates of lymphocyte activation gene-3 expression in renal cell carcinoma.The oncologist · 2026Article
- Decoding T cell exhaustion in the tumour microenvironment.Experimental & molecular medicine · 2026Review
- Tumor immune microenvironment reconstitution in patient-derived organoids enables therapy modeling for NSCLC.Cell reports methods · 2026Article
- A study on the correlation between systemic inflammatory markers in the local tumor immune microenvironment and Porphyromonas gingivalis infection status in patients with oral squamous cell carcinoma.Frontiers in oncology · 2026Article
- LAG3+ CD8+ T cell subset drives HR+/HER2- breast cancer reduction in bispecific antibody armed activated T cell therapy.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Article
- Turning up the heat: CTLA4 blockade in urothelial cancer.Nature reviews. Urology · 2024Review
- Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.Cancers · 2023Review
- Article
- RUNX3 improves CAR-T cell phenotype and reduces cytokine release while maintaining CAR-T function.Medical oncology (Northwood, London, England) · 2023Article
- Aberrant T-cell exhaustion in severe combined immunodeficiency survivors with poor T-cell reconstitution after transplantation.The Journal of allergy and clinical immunology · 2023Article
- High co-expression of immune checkpoint receptors PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT on tumor-infiltrating lymphocytes in early-stage breast cancer.World journal of surgical oncology · 2022Article
- Splenic and PB immune recovery in neoadjuvant treated gastrointestinal cancer patients.International immunopharmacology · 2022Article
- Predictive Markers for Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.Journal of clinical medicine · 2022Review
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- Expression, prognostic significance and therapeutic implications of PD-L1 in gliomas.Neuropathology and applied neurobiology · 2022Review
- Inhibitory Immune Checkpoint Receptors and Ligands as Prognostic Biomarkers in COVID-19 Patients.Frontiers in immunology · 2022Review
- Constructing a thyroid cancer prognostic risk model based on CD8Central-European journal of immunology · 2022Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitory receptors mediate CD8 T-cell hyporesponsiveness against cancer and infectious diseases. PD-1 and CTLA-4 have been extensively studied, and blocking antibodies have already shown clinical benefit for cancer patients. Only little is known on extended co-expression of inhibitory receptors and their ligands. Here we analyzed the expression of eight inhibitory receptors by tumor-antigen specific CD8 T-cells. We found that the majority of effector T-cells simultaneously expressed four or more of the inhibitory receptors BTLA, TIM-3, LAG-3, KRLG-1, 2B4, CD160, PD-1 and CTLA-4. There were major differences depending on antigen-specificity, differentiation and anatomical localization of T-cells. On the other hand, naive T-cells were only single or double positive for BTLA and TIM-3. Extended co-expression is likely relevant for effector T-cells, as we found expression of multiple ligands in metastatic lesions of melanoma patients. Together, our data suggest that naive T-cells are primarily regulated by BTLA and TIM-3, whereas effector cells interact via larger numbers of inhibitory receptors. Blocking multiple inhibitory receptors simultaneously or sequentially may improve T-cell based therapies, but further studies are necessary to clarify the role of each receptor-ligand pair.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.