Artikel
Systemic alterations of the CD4+ T helper cell phenotype in glioma
Systemische Alterationen des CD4+ T-Helfer-Zell Phänotyps in Gliomen
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Veröffentlicht: | 4. Juni 2021 |
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Gliederung
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Objective: Cancer is a systemic disease. Due to the exceedingly rare occurrence of metastasis of cerebral glioma, systemic alterations have, however, not been considered to play a major role in disease progression of glioma. CD4+ T helper (TH) cells orchestrate the adaptive immune response in an antigen-specific, cytokine mediated manner. The aim of our study was to investigate how far cerebral glioma impacts the systemic CD4+ immune repertoire.
Methods: We performed a multi-color flow cytometry analysis of the peripheral blood CD4+ TH cell phenotype and cytokine production in 100 patients with IDHwt, 30 IDHmut and 16 IDHmut 1p19q co-deleted gliomas in comparison with age-matched healthy donors (HD). Data was analyzed using a Fortessa LSR and Diva software. Multiparameter analyses were performed using UMAP analyses and SpadeVizR trees. The study was approved by the local ethics committee (PV4904).
Results: We found a significant skewing of the peripheral immunophenotype in IDHwt glioma patients, showing a TH1 expansion and reduced numbers of T follicular helper cells (TFH), TH1* and mucosa associated invariant T (MAIT) cells (p<0.001), while TH2 and TH17 percentages remained stable compared to IDHmut and HD. Interestingly, although TH1 cells were dominant in IDHwt patients (p<0.01), intracellular cytokine staining showed a distinct reduction of IFNg and TNFa production after in vitro stimulation, while IL-4 was significantly increased compared to HD (p<0.05). No alterations between all groups were observed in IL-2, IL-10 or IL-17 production. Profiling of metabolic surface markers further revealed increased expression of GLUT1 on CD4+ T cells in IDHwt patients, indicating an activated CD4+ repertoire compared to HD.
Conclusion: Taken together, our results show a CD4+ TH cell type specific skewing of the peripheral immune repertoire in patients with IDHwt gliomas. Our data highlights the importance of considering malignant glioma as a disease with profound systemic effects fundamentally altering the immune repertoire in affected patients.