دورية أكاديمية
DNA hypomethylating agents increase activation and cytolytic activity of CD8(+) T cells
| العنوان: | DNA hypomethylating agents increase activation and cytolytic activity of CD8(+) T cells |
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| المؤلفون: | Loo Yau, Helen, Bell, Emma, Ettayebi, Ilias, de Almeida, Felipe Campos, Boukhaled, Giselle M, Shen, Shu Yi, Allard, David, Morancho, Beatriz, Marhon, Sajid A, Ishak, Charles A, Gonzaga, Isabela M, da Silva Medina, Tiago, Singhania, Rajat, Chakravarthy, Ankur, Chen, Raymond, Mehdipour, Parinaz, Pommey, Sandra, Klein, Christian, Amarante-Mendes, Gustavo P, Roulois, David, Arribas, Joaquín, Stagg, John, Brooks, David G, de Carvalho, Daniel D |
| المساهمون: | University Health Network Toronto, ON, Canada, University of Toronto, Universidade de São Paulo = University of São Paulo (USP), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Vall d'Hebron Institute of Oncology Barcelone (VHIO), Vall d'Hebron University Hospital Barcelona, Roche Pharma Research and Early Development Basel (pRED), F. Hoffmann-La Roche Basel, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies (ICREA), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Natural Sciences and Engineering Research Council of Canada, Terry Fox Research Institute, Fundação de Amparo à Pesquisa do Estado de São Paulo, Breast Cancer Research Foundation, Instituto de Salud Carlos III, Canadian Institutes of Health Research |
| المصدر: | ISSN: 1097-2765. |
| بيانات النشر: | HAL CCSD Cell Press |
| سنة النشر: | 2021 |
| المجموعة: | Université de Rennes 1: Publications scientifiques (HAL) |
| مصطلحات موضوعية: | CD8+ T cells, DNA methylation, NFATc1, cytolytic activity, decitabine, epigenetic therapy, granzyme B, killing potential, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; We demonstrate that DNA hypomethylating agent (HMA) treatment can directly modulate the anti-tumor response and effector function of CD8(+) T cells. In vivo HMA treatment promotes CD8(+) T cell tumor infiltration and suppresses tumor growth via CD8(+) T cell-dependent activity. Ex vivo, HMAs enhance primary human CD8(+) T cell activation markers, effector cytokine production, and anti-tumor cytolytic activity. Epigenomic and transcriptomic profiling shows that HMAs vastly regulate T cell activation-related transcriptional networks, culminating with over-activation of NFATc1 short isoforms. Mechanistically, demethylation of an intragenic CpG island immediately downstream to the 3’ UTR of the short isoform was associated with antisense transcription and alternative polyadenylation of NFATc1 short isoforms. High-dimensional single-cell mass cytometry analyses reveal a selective effect of HMAs on a subset of human CD8(+) T cell subpopulations, increasing both the number and abundance of a granzyme B(high), perforin(high) effector subpopulation. Overall, our findings support the use of HMAs as a therapeutic strategy to boost anti-tumor immune response. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33609448; hal-03169813; https://hal.science/hal-03169813Test; PUBMED: 33609448 |
| DOI: | 10.1016/j.molcel.2021.01.038 |
| الإتاحة: | https://doi.org/10.1016/j.molcel.2021.01.038Test https://hal.science/hal-03169813Test |
| رقم الانضمام: | edsbas.7CDA7D47 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.molcel.2021.01.038 |
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