The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans
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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; Öllinger, Rupert; Pfaller, Monika; Wiestler, Benedikt; Rad, Roland; Meyer, Bernhard; Knier, Benjamin; Schmidt-Graf, Friederike; Gempt, Jens; Korn, Thomas.
in: P NATL ACAD SCI USA, Jahrgang 119, Nr. 34, 23.08.2022, S. e2206208119.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans
AU - Mitsdoerffer, Meike
AU - Aly, Lilian
AU - Barz, Melanie
AU - Engleitner, Thomas
AU - Sie, Christopher
AU - Delbridge, Claire
AU - Lepennetier, Gildas
AU - Öllinger, Rupert
AU - Pfaller, Monika
AU - Wiestler, Benedikt
AU - Rad, Roland
AU - Meyer, Bernhard
AU - Knier, Benjamin
AU - Schmidt-Graf, Friederike
AU - Gempt, Jens
AU - Korn, Thomas
PY - 2022/8/23
Y1 - 2022/8/23
N2 - 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.
AB - 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.
KW - Brain Neoplasms/pathology
KW - CD4-Positive T-Lymphocytes/cytology
KW - CD8-Positive T-Lymphocytes/cytology
KW - Flow Cytometry
KW - Glioblastoma/pathology
KW - Humans
KW - Lymphocytes, Tumor-Infiltrating/cytology
KW - T-Lymphocytes, Helper-Inducer/cytology
U2 - 10.1073/pnas.2206208119
DO - 10.1073/pnas.2206208119
M3 - SCORING: Journal article
C2 - 35969754
VL - 119
SP - e2206208119
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 34
ER -