The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the T <subscript>H</subscript> 17 lineage in humans.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 119 (2022-08-23), Heft 34, S. e2206208119
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Zugriff:
Although glioblastoma multiforme (GBM) is not an invariably cold tumor, checkpoint inhibition has largely failed in GBM. In order to investigate T cell-intrinsic properties that contribute to the resistance of GBM to endogenous or therapeutically enhanced adaptive immune responses, we sorted CD4 + and CD8 + T cells from the peripheral blood, normal-appearing brain tissue, and tumor bed of nine treatment-naive patients with GBM. Bulk RNA sequencing of highly pure T cell populations from these different compartments was used to obtain deep transcriptomes of tumor-infiltrating T cells (TILs). While the transcriptome of CD8 + TILs suggested that they were partly locked in a dysfunctional state, CD4 + TILs showed a robust commitment to the type 17 T helper cell (T H 17) lineage, which was corroborated by flow cytometry in four additional GBM cases. Therefore, our study illustrates that the brain tumor environment in GBM might instruct T H 17 commitment of infiltrating T helper cells. Whether these properties of CD4 + TILs facilitate a tumor-promoting milieu and thus could be a target for adjuvant anti-T H 17 cell interventions needs to be further investigated.
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The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the T <subscript>H</subscript> 17 lineage in humans.
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Autor/in / Beteiligte Person: | Mitsdoerffer, M ; Aly, L ; Barz, M ; Engleitner, T ; Sie, C ; Delbridge, C ; Lepennetier, G ; Öllinger, R ; Pfaller, M ; Wiestler, B ; Rad, R ; Meyer, B ; Knier, B ; Schmidt-Graf, F ; Gempt, J ; Korn, T |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 119 (2022-08-23), Heft 34, S. e2206208119 |
Veröffentlichung: | Washington, DC : National Academy of Sciences, 2022 |
Medientyp: | academicJournal |
ISSN: | 1091-6490 (electronic) |
DOI: | 10.1073/pnas.2206208119 |
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