IRF4 instructs effector Treg differentiation and immune suppression in human cancer
| Autor: | Ajithkumar Vasanthakumar, Agnese Losurdo, Emilia Maria Cristina Mazza, Axel Kallies, Simone Puccio, Jonas Blume, Massimiliano Pagani, Giorgia Alvisi, Federico Colombo, Marco Alloisio, Egesta Lopci, Rahul Roychoudhuri, Elisa Paoluzzi Tomada, Clelia Peano, Alice Scarpa, Jolanda Brummelman, Giulia Veronesi, Pierluigi Novellis, Marinos Kallikourdis, Enrico Lugli, Veronica Zanon |
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| Přispěvatelé: | Alvisi, G, Brummelman, J, Puccio, S, Mazza, E. M. C, Tomada, E. P, Losurdo, A, Zanon, V, Peano, C, Colombo, F. S, Scarpa, A, Alloisio, M, Vasanthakumar, A, Roychoudhuri, R, Kallikourdis, M, Pagani, M, Lopci, E, Novellis, P, Blume, J, Kallies, A, Veronesi, G, Lugli, E. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Cellular differentiation medicine.medical_treatment Biology T-Lymphocytes Regulatory 03 medical and health sciences Mice 0302 clinical medicine Immune system Cancer immunotherapy Neoplasms BATF medicine Tumor Microenvironment Animals Humans Aged Aged 80 and over Tumor microenvironment Effector Cell Differentiation General Medicine Middle Aged Acquired immune system Neoplasm Proteins 030104 developmental biology 030220 oncology & carcinogenesis Interferon Regulatory Factors Cancer research IRF4 Research Article |
| Zdroj: | J Clin Invest Journal of Clinical Investigation, 130, 3137-3150 Journal of Clinical Investigation, 130, 6, pp. 3137-3150 |
| ISSN: | 0021-9738 |
| Popis: | The molecular mechanisms responsible for the high immunosuppressive capacity of CD4(+) Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non–small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4(+) effector Tregs with superior suppressive activity. In contrast to the IRF4(–) counterparts, IRF4(+) Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4(+) Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type. |
| Databáze: | OpenAIRE |
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