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The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the T(H)17 lineage in humans

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(+)...

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Detalles Bibliográficos
Autores principales: Mitsdoerffer, Meike, Aly, Lilian, Barz, Melanie, Engleitner, Thomas, Sie, Christopher, Delbridge, Claire, Lepennetier, Gildas, Öllinger, Rupert, Pfaller, Monika, Wiestler, Benedikt, Rad, Roland, Meyer, Bernhard, Knier, Benjamin, Schmidt-Graf, Friederike, Gempt, Jens, Korn, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407554/
https://www.ncbi.nlm.nih.gov/pubmed/35969754
http://dx.doi.org/10.1073/pnas.2206208119
Descripción
Sumario: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.