期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：34
DOI：10.1073/pnas.2206208119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Glioblastoma multiforme (GBM) has been impervious to immune interventional therapies. Here, we analyzed the transcriptome of highly pure CD4
+ and CD8
+ T cells from the tumor bed, normal-appearing brain tissue, and peripheral blood of treatment-naive GBM patients. While the transcriptome of tumor-infiltrating CD8
+ T cells was consistent with a potentially robust antitumor response, tumor-infiltrating CD4
+ T cells showed a strong commitment to the T
H17 lineage. Since intratumoral T
H17 cells might exert a dominant-negative function as to a productive antitumor response, our data suggest that a site-directed anti-T
H17 intervention may be a prerequisite for efficient antitumor immunity in GBM.
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
H17) 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
H17 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
H17 cell interventions needs to be further investigated.
关键词：englioblastoma multiformeTH17 cellstissue residencyRNA sequencinggene set enrichment analysis
