Human allogenic gamma delta T cells kill patient-derived glioblastoma cells expressing high levels of DNAM-1 ligands

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Adoptive transfer of gamma delta T cells is a novel immunotherapeutic approach to glioblastoma. Few recent studies have shown the efficacy of gamma delta T cells against glioblastoma, but no previous studies have identified the ligand-receptor interactions between gamma delta T cells and glioblastoma cells. Here, we identify those ligand-receptor interactions and provide a basis for using gamma delta T cells to treat glioblastoma. V gamma 9V delta 2 T cells were generated from peripheral blood mononuclear cells of healthy donors using artificial antigen presenting cells. MICA, ULBP, PVR and Nectin-2 expression in 10 patient-derived glioblastoma (PDG) cells were analyzed. The in vitro cytokine secretion from the gamma delta T cells and their cytotoxicity toward the PDG cells were also analyzed. The in vivo anti-tumor effects were evaluated using a U87 orthotopic xenograft glioblastoma model. Expression of ligands and cytotoxicity of the gamma delta T cells varied among the PDG cells. IFN-gamma and Granzyme B secretion levels were significantly higher when gamma delta Tcells were co-cultured with high-susceptible PDG cells than when they were co-cultured with low-susceptible PDG cells. Cytotoxicity correlated significantly with the expression levels of DNAM-1 ligands of the PDG cells. Blocking DNAM-1 resulted in a decrease in gamma delta T cell-mediated cytotoxicity and cytokine secretion. Intratumoral injection of gamma delta T cells showed anti-tumor effects in an orthotopic mouse model. Allogenic gamma delta T cells showed potent anti-tumor effects on glioblastoma in a DNAM-1 axis dependent manner. Our findings will facilitate the development of clinical strategies using gamma delta T cells for glioblastoma treatment.
Publisher
TAYLOR & FRANCIS INC
Issue Date
2022-12
Language
English
Article Type
Article
Citation

ONCOIMMUNOLOGY, v.11, no.1

ISSN
2162-4011
DOI
10.1080/2162402X.2022.2138152
URI
http://hdl.handle.net/10203/299554
Appears in Collection
MSE-Journal Papers(저널논문)
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