NKG2D Controls Natural Reactivity of Vγ9Vδ2 T Lymphocytes against Mesenchymal Glioblastoma Cells.
Clin Cancer Res, 2019/12/01;25(23):7218-7228.
Chauvin C[1, 2], Joalland N[1, 2], Perroteau J[1, 2], Jarry U[1, 2], Lafrance L[1, 2], Willem C[1, 3], Retière C[1, 3], Oliver L[1, 4], Gratas C[1, 4], Gautreau-Rolland L[1, 2], Saulquin X[1, 2], Vallette FM[1, 2, 5], Vié H[1, 2], Scotet E[6, 2], Pecqueur C[6, 2]
Affiliations
PMID: 31506386DOI: 10.1158/1078-0432.CCR-19-0375
Impact factor: 13.801
Abstract
purpose: Cellular immunotherapies are currently being explored to eliminate highly invasive and chemoradioresistant glioblastoma (GBM) cells involved in rapid relapse. We recently showed that concomitant stereotactic injections of nonalloreactive allogeneic Vγ9Vδ2 T lymphocytes eradicate zoledronate-primed human GBM cells. In the present study, we investigated the spontaneous reactivity of allogeneic human Vγ9Vδ2 T lymphocytes toward primary human GBM cells, in vitro and in vivo, in the absence of any prior sensitization.
experimental design: Through functional and transcriptomic analyses, we extensively characterized the immunoreactivity of human Vγ9Vδ2 T lymphocytes against various primary GBM cultures directly derived from patient tumors.
results: We evidenced that GBM cells displaying a mesenchymal signature are spontaneously eliminated by allogeneic human Vγ9Vδ2 T lymphocytes, a reactivity process being mediated by γδ T-cell receptor (TCR) and tightly regulated by cellular stress-associated NKG2D pathway. This led to the identification of highly reactive Vγ9Vδ2 T lymphocyte populations, independently of a specific TCR repertoire signature. Moreover, we finally provide evidence of immunotherapeutic efficacy in vivo, in the absence of any prior tumor cell sensitization.
conclusions: By identifying pathways implicated in the selective natural recognition of mesenchymal GBM cell subtypes, accounting for 30% of primary diagnosed and 60% of recurrent GBM, our results pave the way for novel targeted cellular immunotherapies.
MeSH terms
Animals; Apoptosis; Cell Proliferation; Glioblastoma; Humans; Mesenchymal Stem Cells; Mice; Mice, Inbred NOD; Mice, SCID; NK Cell Lectin-Like Receptor Subfamily K; Prognosis; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocyte Subsets; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
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