IMMU-17. SYSTEMIC IMMUNOSUPPRESSION OF CD4+ T HELPER CELLS IN GLIOMA. (12th November 2021)

• Record Type: Journal Article
• Authors: Mohme, Malte; Maire, Cecile; Rünger, Alessandra; Glau, Laura; Tolosa, Eva; Westphal, Manfred; Lamszus, Katrin
• Is Part Of: Neuro-oncology. Volume 23: Supplement 6(2021)
• Page Start: vi95
• Page End: vi95
• Publication Date: 2021-11-12
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab196.376
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: 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. We therefore analyzed 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). We found a significant skewing of the peripheral phenotype in IDHwt glioma patients, showing a TH 1 expansion and reduced numbers of T follicular helper cells (TFH ), TH 1* and mucosa associated invariant T (MAIT) cells, while TH 2 and TH 17 percentages remained stable compared to IDHmut and HD. Interestingly, although TH 1 cells were dominant in IDHwt patients, 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. No alterations between all groups were observed in IL-2, IL-10 or IL-17 production. Profiling of metabolic surface markers further revealed three distinct groups of CD4+ T cells which are altered in IDHwt patients, indicating a metabolic shift in the CD4+ repertoire compared to HD. 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 systemic disease that fundamentally alters the immune repertoire in affected patients.