Dendritic cells cross-talk with tumour antigen-specific CD8+ T cells, Vγ9γδT cells and Vα24NKT cells in patients with glioblastoma multiforme and in healthy donors

Abstract

SummaryThe finding that dendritic cells (DCs) orchestrate innate and adaptive immune responses has stimulated research on harnessing DCs for developing more effective vaccines for DC therapy. The expression of cytomegalovirus (CMV) antigens in glioblastoma multiforme (GBM) presents a unique opportunity to target these viral proteins for tumour immunotherapy. Here, we demonstrate that Vγ9γδT cells, innate immune cells activated by zoledronate (Z) and Vα24 natural killer (Vα24NK) cells, innate/adaptive immune cells activated by α‐galactosylceramide (G) can link innate and adaptive immunities through cross‐talk with interferon (IFN) DCs from patients with glioblastoma multiforme (GBM) and healthy donors in a manner that can amplify the activation and proliferation of CMVpp65‐specific CD8+ T cells. The IFN DCs derived from patients with GBM used in this study express lower levels of programmed cell death ligand (PD)‐L1 and PD‐L2 and higher levels of C‐C receptor 7 (CCR7) than the most commonly used mature interleukin (IL)‐4 DCs. The expression level of programmed cell death 1 (PD‐1) on CD8+ T cells, including CMVpp65‐specific CD8+ T cells, expanded by IFN DCs pulsed with the CMVpp65‐peptide and Z plus G (IFN DCs/P+Z+G), was lower than that expanded by IFN DCs pulsed with the peptide alone (IFN DCs/P). Multi‐functional T cells, including human leucocyte antigen (HLA)‐A*0201‐restricted CMVpp65‐specific CD8+ T cells, Vγ9γδT cells and Vα24NKT cells, efficiently kill the HLA‐A*0201‐positive GBM cell line expressing CMVpp65 protein (T98G). These findings indicate that DC therapy using IFN DCs/P+Z+G and/or CTL therapy using CMVpp65‐specific CD8+ T cells expanded by IFN DCs/P+Z+G may lead to a good clinical outcome for patients with GBM.

Oestrogen and zoledronic acid driven changes to the bone and immune environments: Potential mechanisms underlying the differential anti-tumour effects of zoledronic acid in pre- and post-menopausal conditions

“…This is in stark contrast to the effects of ZOL on PD-1 expression. ZOL downregulates PD-1 expression on Tregs, which both reduces iTreg conversion and reduces the ability of Tregs to functionally supress T effector cells in the tumour microenvironment [100] . Furthermore, ZOL was shown to inhibit the proliferation and migratory capacity of Treg cells which would reduce their capacity to infiltrate the tumour microenvironment.…”

Interaction network of immune‑associated genes affecting the prognosis of patients with glioblastoma

“…This suggests that a high-risk score may be associated with a secondary elevation of CD4 T cells, dendritic cells and macrophages, as well as a secondary reduction of CD8 T cells. Previous studies have indicated that CD8 T cells and dendritic cells have a positive role in the development of a normal body ( 40-44 ). This may indicate that an increase in the risk score may cause a secondary decrease in CD8 T cells, thereby promoting tumor development.…”

Targeting the dendritic cell-T cell axis to develop effective immunotherapies for glioblastoma

“…Likewise, Liu et al conclude that the future of glioblastoma treatments lies in a multifaceted immune response (129). Eiraku et al had a similar conclusion that combinations of DCV and CAR-T cells with ICI may provide a better outcome (53).…”