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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, Vol. 119, No. 34, 23.08.2022, p. e2206208119.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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 2022, 'The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans', P NATL ACAD SCI USA, vol. 119, no. 34, pp. e2206208119. https://doi.org/10.1073/pnas.2206208119

APA

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. (2022). The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans. P NATL ACAD SCI USA, 119(34), e2206208119. https://doi.org/10.1073/pnas.2206208119

Vancouver

Mitsdoerffer M, Aly L, Barz M, Engleitner T, Sie C, Delbridge C et al. The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans. P NATL ACAD SCI USA. 2022 Aug 23;119(34):e2206208119. https://doi.org/10.1073/pnas.2206208119

Bibtex

@article{3de7df4d8dda432f928fb2cf3a081ec4,
title = "The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans",
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 (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.",
keywords = "Brain Neoplasms/pathology, CD4-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/cytology, Flow Cytometry, Glioblastoma/pathology, Humans, Lymphocytes, Tumor-Infiltrating/cytology, T-Lymphocytes, Helper-Inducer/cytology",
author = "Meike Mitsdoerffer and Lilian Aly and Melanie Barz and Thomas Engleitner and Christopher Sie and Claire Delbridge and Gildas Lepennetier and Rupert {\"O}llinger and Monika Pfaller and Benedikt Wiestler and Roland Rad and Bernhard Meyer and Benjamin Knier and Friederike Schmidt-Graf and Jens Gempt and Thomas Korn",
year = "2022",
month = aug,
day = "23",
doi = "10.1073/pnas.2206208119",
language = "English",
volume = "119",
pages = "e2206208119",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "34",

}

RIS

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 -