ArticleInternational journal of cancer2014
Selective targeting of Toll-like receptors and OX40 inhibit regulatory T-cell function in follicular lymphoma.
Article in International journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Absolute numbers of regulatory T cells and neutrophils in corticosteroid-free patients are predictive for response to bevacizumab in recurrent glioblastoma patients.Cancer immunology, immunotherapy : CII · 2019Trial
- Tumor-infiltrating mast cells confer resistance to immunotherapy in pancreatic cancer.iScience · 2024Article
- Engineered Lactococcus lactis secreting Flt3L and OX40 ligand for in situ vaccination-based cancer immunotherapy.Nature communications · 2022Article
- The characteristics of the immune cell profiles in peripheral blood in cholangiocarcinoma patients.Hepatology international · 2021Article
- In vivo NIR-II structured-illumination light-sheet microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- The Complex Role of Regulatory T Cells in Immunity and Aging.Frontiers in immunology · 2020Review
- Next-Generation Antibody Therapeutics: Discovery, Development and Beyond: highlights of the third annual conference of the Chinese Antibody Society.Antibody therapeutics · 2019Article
- Stimulating T Cells Against Cancer With Agonist Immunostimulatory Monoclonal Antibodies.International review of cell and molecular biology · 2019Review
- Proteomic changes of CD4Experimental and therapeutic medicine · 2017Article
- TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines.Current opinion in immunology · 2017Review
- Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients.Scientific reports · 2016Article
- [Donor- derived CD19 chimeric antigen receptor T cells for relapsed B cell malignancies after allogeneic hematopoietic stem cell transplantations].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2016Article
- Targeting the tumor niche to treat cancer.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Strategies for combining immunotherapy with radiation for anticancer therapy.Immunotherapy · 2015Review
- Challenges and opportunities in the development of combination immunotherapy with OX40 agonists.Expert opinion on biological therapyReview
- Article
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Immunotherapeutic strategies are promising approaches for the treatment of follicular lymphoma (FL). However, their efficacy may be limited by immunosuppressive elements in the immune system and tumor microenvironment. Therefore, strategies to reverse the effects of the immunosuppressive elements are needed. We observed that regulatory T cells (Tregs) were increased in the peripheral blood at diagnosis and persisted in high numbers after induction of clinical remission with a cyclophosphamide and doxorubicin-containing chemotherapy regimen in FL patients. High levels of peripheral blood Tregs prior to therapy were associated with decreased progression-free survival in FL patients treated with either chemotherapy or combination immunotherapy that targeted CD20 and PD-1 with monoclonal antibodies rituximab and pidilizumab, respectively. Intratumoral and peripheral blood Tregs potently suppressed autologous antitumor effector T cells in FL. However, the effects of FL Tregs could be reversed by triggering Toll-like receptors (TLR) with TLR ligands Pam3 CSK4 (TLR 1/2), flagellin (TLR 5), and CpG-B (TLR 9), and/or OX40. The TLR ligands synergized with each other as well as OX40 signaling to inhibit Tregs. Furthermore, they restored the function of FL tumor-specific effector T cells. Our results suggest that a state of tolerance exists in FL patients at diagnosis and after induction of clinical remission, and agents that activate TLRs 1/2, 5, and 9, and OX40 may serve as adjuvants to enhance the efficacy of antitumor immunotherapeutic strategies and preventive vaccines against infectious diseases in these patients.
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