ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 80 citations in OpenAlex.
- Disrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer.Clinical and experimental immunology · 2019Trial
- Tumor Infiltrating Lymphocytes in Cutaneous Squamous Cell Carcinoma-A Systematic Review.Dermatopathology (Basel, Switzerland) · 2026Review
- Advances in Targeted and Immunotherapy for High-Risk Cutaneous Malignancies.Oncology research · 2026Review
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Targeting VISTA as a novel immunotherapy for skin cancer.Frontiers in immunology · 2026Review
- The OX40-OX40L Co-stimulatory pathway in dermatology: emerging frontiers for therapeutic approaches.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- A phase I study of the OX40 agonist BGB-A445 with or without tislelizumab, an anti-PD-1 monoclonal antibody, in patients with advanced solid tumors: dose-escalation results.Cancer chemotherapy and pharmacology · 2025Article
- Enhanced metastasis risk prediction in cutaneous squamous cell carcinoma using deep learning and computational histopathology.NPJ precision oncology · 2025Article
- Anti-OX40 antibody BAT6026 in patients with advanced solid tumors: A multi-center phase I study.iScience · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Current and Emerging Insights into the Causes, Immunopathogenesis, and Treatment of Cutaneous Squamous Cell Carcinoma.Cancers · 2025Review
- Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC).Cells · 2024Review
- OX40/OX40 ligand and its role in precision immune oncology.Cancer metastasis reviews · 2024Review
- The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review.Cancers · 2024Review
- Circulating Regulatory T Cells: A Novel Marker Associated with Liver Metastasis and the Treatment Response of Transarterial Embolization in Gastroenteropancreatic Neuroendocrine Tumors.Neuroendocrinology · 2024Article
- Agonistic Bivalent Human scFvs-Fcγ Fusion Antibodies to OX40 Ectodomain Enhance T Cell Activities against Cancer.Vaccines · 2023Article
- Advanced Cutaneous Squamous Cell Carcinoma Management in Immunotherapy Era: Achievements and New Challenges.Dermatology practical & conceptual · 2023Review
- Article
- Programmed cell death-1 receptor-mediated regulation of TbetProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Immunosenescence and Skin: A State of Art of Its Etiopathogenetic Role and Crucial Watershed for Systemic Implications.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeCutaneous squamous cell carcinoma (cSCC) is the most common human cancer with metastatic potential. Despite T cells accumulating around cSCCs, these tumors continue to grow and persist. To investigate reasons for failure of T cells to mount a protective response in cSCC, we focused on regulatory T cells (Tregs) as this suppressive population is well represented among the infiltrating lymphocytes. EXPERIMENTAL
designFlow cytometry was conducted on cSCC lymphocytes and in vitro functional assays were performed using sorted tumoral T cells. Lymphocyte subsets in primary cSCCs were quantified immunohistochemically.
resultsFOXP3(+) Tregs were more frequent in cSCCs than in peripheral blood (P < 0.0001, n = 86 tumors). Tumoral Tregs suppressed proliferation of tumoral effector CD4(+) (P = 0.005, n = 10 tumors) and CD8(+) T cells (P = 0.043, n = 9 tumors) and inhibited IFNγ secretion by tumoral effector T cells (P = 0.0186, n = 11 tumors). The costimulatory molecule OX40 was expressed predominantly on tumoral Tregs (P < 0.0001, n = 15 tumors) and triggering OX40 with an agonist anti-OX40 antibody overcame the suppression exerted by Tregs, leading to increased tumoral effector CD4(+) lymphocyte proliferation (P = 0.0098, n = 10 tumors). Tregs and OX40(+) lymphocytes were more abundant in primary cSCCs that metastasized than in primary cSCCs that had not metastasized (n = 48 and n = 49 tumors, respectively).
conclusionsTregs in cSCCs suppress effector T-cell responses and are associated with subsequent metastasis, suggesting a key role for Tregs in cSCC development and progression. OX40 agonism reversed the suppressive effects of Tregs in vitro, suggesting that targeting OX40 could benefit the subset of cSCC patients at high risk of metastasis. Clin Cancer Res; 22(16); 4236-48. ©2016 AACR.
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