ArticleInternational immunology2009
PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells.
Article in International immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed, 273 citations in OpenAlex.
- Trial
- CTLA-4: a promising immunosuppressive immune checkpoint in prostate cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Identification of the Molecular Subtype and Prognostic Characteristics of Breast Cancer Based on Tumor-Infiltrating Regulatory T Cells.The breast journal · 2025Article
- Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3Nature communications · 2024Article
- Arginine vasopressin (AVP) treatment increases the expression of inhibitory immune checkpoint molecules in monocyte-derived dendritic cells.Immunologic research · 2024Article
- Regulatory T cells in immune checkpoint blockade antitumor therapy.Molecular cancer · 2024Review
- Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC.BMC cancer · 2024Article
- The role of programmed death receptor (PD-)1/PD-ligand (L)1 in periodontitis and cancer.Periodontology 2000 · 2024Review
- Lymphocyte T Subsets and Outcome of Immune Checkpoint Inhibitors in Melanoma Patients: An Oncologist's Perspective on Current Knowledge.International journal of molecular sciences · 2024Review
- Review
- Impact of immunosenescence and inflammaging on the effects of immune checkpoint inhibitors.Cancer pathogenesis and therapy · 2024Review
- A new target of radiotherapy combined with immunotherapy: regulatory T cells.Frontiers in immunology · 2023Review
- Implications of regulatory T cells in anti-cancer immunity: from pathogenesis to therapeutics.Heliyon · 2022Review
- Excessive immunosuppression by regulatory T cells antagonizes T cell response to schistosome infection in PD-1-deficient mice.PLoS pathogens · 2022Article
- Identification of a CD4Human immunology · 2022Article
- Immune Checkpoint Inhibitors Induced Hepatotoxicity; Gastroenterologists' Perspectives.Middle East journal of digestive diseases · 2022Review
- Checkpoint Inhibitors and the Gut.Journal of clinical medicine · 2022Review
- Triggering of lymphocytes by CD28, 4-1BB, and PD-1 checkpoints to enhance the immune response capacities.PloS one · 2022Article
- Baseline immune signature score of Tregs × HLA-DRFrontiers in immunology · 2022Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. However, the underlying mechanisms by which they impact antigen-specific CD8(+) immune responses in cancer patients and how they interact with each other under physiologic conditions remain unclear. Herein, we examined the relationship of PD-1 and its abrogation to the function of Treg in patients with melanoma using short-term in vitro assays to generate melanoma-specific T cells. We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. Programmed death ligand (PD-L) 1 expression was also detected on patients' Treg. PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. PD-1 blockade also resulted in down-regulation of intracellular FoxP3 expression by Treg. These data suggest that PD-1 is importantly implicated in the regulation of Treg function in melanoma patients.
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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.