التفاصيل البيبلوغرافية
| العنوان: |
IRF4 instructs effector Treg differentiation and immune suppression in human cancer. |
| المؤلفون: |
Alvisi, Giorgia1, Brummelman, Jolanda1, Puccio, Simone1, Mazza, Emilia M. C.1, Tomada, Elisa Paoluzzi1, Losurdo, Agnese1,2, Zanon, Veronica1, Peano, Clelia3,4, Colombo, Federico S.5, Scarpa, Alice1, Alloisio, Marco6,7, Vasanthakumar, Ajithkumar8, Roychoudhuri, Rahul9, Kallikourdis, Marinos10, Pagani, Massimiliano11, Lopci, Egesta12, Novellis, Pierluigi6, Blume, Jonas8, Kallies, Axel8, Veronesi, Giulia6 |
| المصدر: |
Journal of Clinical Investigation. Jun2020, Vol. 130 Issue 6, p3137-3150. 14p. 5 Graphs. |
| مصطلحات موضوعية: |
*IMMUNOSUPPRESSION, *T cells, *NON-small-cell lung carcinoma, *SUPPRESSOR cells, *TUMOR microenvironment, *CANCER cell differentiation, *ANIMAL experimentation, *CELL differentiation, *CELL physiology, *COMPARATIVE studies, *RESEARCH methodology, *MEDICAL cooperation, *MICE, *PROTEINS, *RESEARCH, *TUMORS, *EVALUATION research |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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