The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans

Mitsdoerffer, Meike; Aly, Lilian; Barz, Melanie; Engleitner, Thomas; Sie, Christopher; Delbridge, Claire; Lepennetier, Gildas; Oellinger, Rupert; Pfaller, Monika; Wiestler, Benedikt; Rad, Roland; Meyer, Bernhard; Knier, Benjamin; Schmidt-Graf, Friederike; Gempt, Jens und Korn, Thomas (2022): The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans. In: Proceedings of the National Academy of Sciences of the United States of America, Bd. 119, Nr. 34, e2206208119

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198