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

PNAS article from the Korn lab (B06)

22.07.2022

Meike Mitsdoerffer, Lilian Alya, Melanie Barz, Thomas Engleitner, Christopher Sie, Claire Delbridge, Gildas Lepennetier, Rupert Öllinger, Monika Pfaller , Benedikt Wiestler, Roland Rad, Bernhard Meyerc, Benjamin Knier , Friederike Schmidt-Graf, Jens Gempt and Thomas Korn (2022) PNAS Vol 119:34 e2206208119. https://doi.org/10.1073/pnas.2206208119

 

Abstract cited directly from the article:

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 (TH17) 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 TH17 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-TH17 cell interventions needs to be further investigated.


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