γδ T Cells in Peripheral Blood of Glioma Patients

Abstract

BackgroundGlioma is a common brain malignancy, but the effects of the γδ T cells and their subsets in peripheral blood in patients with glioma have not been reported.Material/MethodsFlow cytometry was used to analyze the functions and expressions of δ T cells and their subsets in peripheral blood in healthy controls and patients with glioma. The Vδ2 T cells and the activation of killing function-related signaling pathway were analyzed by Western blot assay; the immunosuppressive functions of Vδ1 T cells were detected by CFSE proliferation assay; and the Vδ2 T cell killing functions were detected by killing assay.ResultsCompared with the healthy controls, the ratio of Vδ1 T cells was significantly increased and the ratio of Vδ2 T cells was significantly decreased. After in vitro culture and anti-TCR γδ antibody stimulation and in the presence of IL-2, in the patients with glioma, the Vδ1 T cells dominated and Vδ2 T cells were scarce. Flow cytometry staining showed that expression of immunosuppression-related molecules on the Vδ1 T cell surface was significantly increased, while the expression of killing function-related molecules and the activation of killing function-related signaling pathway in the Vδ2 T cells were significantly decreased. Functional test results showed that the immunosuppressive function of Vδ1T cells was enhanced and the killing function of Vδ1T cells was reduced.ConclusionsThe ratio and function changes of Vδ1 T cells and Vδ2 T cells are possibly associated with the pathogenesis of glioma.

Phenotypic characterization of human peripheral γδT‐cell subsets in glioblastoma

“…Additionally, it was shown that patients with renal carcinoma who had a peripheral γδT cell ratio of >8.7% before surgery had better overall survival in a follow‐up of 137 months 14 . Regarding the γδT cell subsets, similar to the results of Yue et al, 8 our series showed an increase of Vδ1 T cells in patients with glioma and a decrease of Vδ2 T cells. The variation of these two subsets depends also on the expression degree of their markers.…”

“…Indeed, Vδ1 T cells significantly increased while Vδ2 decreased in glioblastoma. Similar to our findings, the total γδT cells in the peripheral blood of patients with glioma did not show any significant change 8 . Bryant et al reported a depletion of γδT cells in patients with cancer including high‐grade gliomas 9 .…”

“…Similar to our findings, the total γδT cells in the peripheral blood of patients with glioma did not show any significant change. 8 Bryant et al reported a depletion of γδT cells in patients with cancer including high-grade gliomas. 9 This depletion seems to correspond to a failure of the antitumor response leading to their elimination from the circulation by the activatinginduced cell death (AICD) process, as suggested by Ferrarini et al, who first showed that γδT cells are activated in culture, upon contact with Daudi lymphoma cells but subsequently succumb to AICD.…”

“…47 Yue et al have shown that the expression of immunosuppression-related molecules on peripheral Vδ1 T cells in glioma patients was increased, with a significant immunosuppressive function. 8 The interaction of PD-1 with PD-L1 alters the survival and proliferation of γδT cells, as well as IL-2 production through the PTEN (protein phosphatase and TENsin homolog) signaling pathway. 48 On the other hand, BTLA, another inhibitory receptor structurally related to PD-1 and cytotoxic-T-lymphocyteantigen 4 (CTLA-4) 7 was downregulated on the γδT cells of our patients with glioblastoma.…”

Glioblastoma Microenvironment and Cellular Interactions

“…γδ T cells are expressing more subpopulations in the blood and the tumor tissues [ 271 ]. GBM patients have an increased number of circulating Vδ1T cells (with immunosuppressive functions) and significantly decreased circulating Vδ2T cells (with cytotoxic activities) [ 236 , 272 ].…”