ArticleThe Journal of clinical investigation2014
Dynamic Treg interactions with intratumoral APCs promote local CTL dysfunction.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03447678 (Phase II Study to Test Pembrolizumab), which is not on this map. Cited by 146 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Phase II Study to Test Pembrolizumab (MK-3475) in First Line Treatment of Advanced NSCLC Patients With PD-L1 Low Tumors (<50%)_ PEOPLE TRIAL (Pembrolizumab in Pd-L1 Low Expressors).
Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 234 citations in OpenAlex.
- Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review.Cell communication and signaling : CCS · 2021Pooled it
- Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives.Chinese medical journal · 2026Review
- The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM.Cell · 2026Article
- Endoplasmic reticulum stress-induced histone lactylation mediating immune escape of gastric cancer via PDIA6 overexpression in dendritic cells.Cell death & disease · 2026Article
- Positioning and reversible suppression of CCR7Immunity · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- The roles of cell cycle proteins in regulating the tumor immune microenvironment.Genes & diseases · 2026Review
- Tumor Microenvironment-Responsive Nanoparticles for Pancreatic Cancer Imaging and Treatment.International journal of nanomedicine · 2026Review
- The dual role of T cells in solid organ transplant rejection and immune tolerance.Frontiers in immunology · 2026Review
- Clostridium leptum attenuates allergic airway inflammation via tDC‒Treg axis activation in a murine model of gut dysbiosis-associated asthma.Scientific reports · 2025Article
- Non-Histone Lysine Modifications in Tumor Microenvironment: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Integrating Mathematical and Mouse Models Identifies T Regulatory Cell Influx as A Key Determinant of Acquired Resistance to PD-1 Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Roles of the gut microbiota in hepatocellular carcinoma: from the gut dysbiosis to the intratumoral microbiota.Cell death discovery · 2025Review
- Intravital Imaging of Immune Responses in the Cancer Microenvironment.Cancer medicine · 2025Review
- Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells.Nature biomedical engineering · 2025Article
- Architects of immunity: How dendritic cells shape CD8Science immunology · 2025Review
- AL161431.1 is identified as a biomarker for bladder cancer progression and immunotherapy response.Scientific reports · 2025Article
- Article
- Cold and hot tumors: from molecular mechanisms to targeted therapy.Signal transduction and targeted therapy · 2024Review
- Innate immune cells in tumor microenvironment: A new frontier in cancer immunotherapy.iScience · 2024Review
86 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tregs control various functions of effector T cells; however, where and how Tregs exert their immunomodulatory effects remain poorly understood. Here we developed a murine model of adoptive T cell therapy and found that Tregs induce a dysfunctional state in tumor-infiltrating CTLs that resembles T cell exhaustion and is characterized by low expression of effector cytokines, inefficient cytotoxic granule release, and coexpression of coinhibitory receptors PD-1 and TIM-3. Induction of CTL dysfunction was an active process, requiring local TCR signals in tumor tissue. Tregs infiltrated tumors only subsequent to Ag-dependent activation and expansion in tumor-draining LNs; however, Tregs also required local Ag reencounter within tumor tissue to induce CTL dysfunction and prevent tumor rejection. Multiphoton intravital microscopy revealed that in contrast to CTLs, Tregs only rarely and briefly interrupted their migration in tumor tissue in an Ag-dependent manner and formed unstable tethering-interactions with CD11c+ APCs, coinciding with a marked reduction of CD80 and CD86 on APCs. Activation of CTLs by Treg-conditioned CD80/86lo DCs promoted enhanced expression of both TIM-3 and PD-1. Based on these data, we propose that Tregs locally change the costimulatory landscape in tumor tissue through transient, Ag-dependent interactions with APCs, thus inducing CTL dysfunction by altering the balance of costimulatory and coinhibitory signals these cells receive.
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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.