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Title:
Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients | Cancer Immunology, Immunotherapy
Description:
CD4+CD25+ regulatory T cells are involved in the prevention of autoimmune diseases and in tumor-induced tolerance. We previously demonstrated in tumor-bearing rodents that one injection of cyclophosphamide could significantly decrease both numbers and suppressive functions of regulatory T cells, facilitating vaccine-induced tumor rejection. In humans, iterative low dosing of cyclophosphamide, referred to as âmetronomicâ therapy, has recently been used in patients with advanced chemotherapy resistant cancers with the aim of reducing tumor angiogenesis. Here we show that oral administration of metronomic cyclophosphamide in advanced cancer patients induces a profound and selective reduction of circulating regulatory T cells, associated with a suppression of their inhibitory functions on conventional T cells and NK cells leading to a restoration of peripheral T cell proliferation and innate killing activities. Therefore, metronomic regimen of cyclophosphamide does not only affect tumor angiogenesis but also strongly curtails immunosuppressive regulatory T cells, favoring a better control of tumor progression. Altogether these data support cyclophosphamide regimen as a valuable treatment for reducing tumor-induced immune tolerance before setting to work anticancer immunotherapy.
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article, cancer, cells, google, scholar, cas, pubmed, regulatory, cyclophosphamide, metronomic, ghiringhelli, patients, françois, tumor, immunotherapy, cdcd, cell, menard, zitvogel, therapy, chemotherapy, immune, res, privacy, cookies, content, functions, puig, martin, solary, chauffert, access, immunol, blood, author, function, data, information, publish, search, regimen, roux, treatment, france, log, journal, research, immunology, september, cedric,
Topics {âïž}
t-cell-dependent immune defense month download article/chapter human regulatory cd4+cd25+ late-stage ovarian cancer eric solary cyclophosphamide-resistant murine tumor axel le cesne article cancer immunology faculté de médecine author information authors cd4+cd25+ regulatory regulatory cd4+cd25+ t-suppressor function metronomic chemotherapy regimens full article pdf tumor-induced tolerance reducing tumor angiogenesis cd4+cd25hi regulatory privacy choices/manage cookies specific antitumor immunotherapy metronomic regimen tumor-bearing rodents affect tumor angiogenesis work anticancer immunotherapy author correspondence enhanced immune response low dose cyclophosphamide low-dose cyclophosphamide cyclophosphamide induces type check access instant access article ghiringhelli optimal biologic dose nk effector functions interferon alpha-induced intermittent bolus cyclophosphamide european economic area innate killing activities related subjects facs-isolated populations conejo-garcia jr exosome-based vaccines maximum antiangiogenic activity chronic lymphocytic leukaemia institut gustave roussy nk cells leading iterative low dosing conditions privacy policy predicts reduced survival murine melanoma model
Questions {â}
- Gasparini G (2001) Metronomic scheduling: the future of chemotherapy?
- T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?
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Cancer Research
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