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

Autor: Haeyoun Choi, Yunkyung Lee, Soon A Park, Ji Hyeon Lee, Junseong Park, Jang Hyun Park, Heung Kyu Lee, Tai-Gyu Kim, Sin-Soo Jeun, Stephen Ahn
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: OncoImmunology, Vol 11, Iss 1 (2022)
Druh dokumentu: article
ISSN: 2162402X
2162-402X
DOI: 10.1080/2162402X.2022.2138152
Popis: Adoptive transfer of γδ T cells is a novel immunotherapeutic approach to glioblastoma. Few recent studies have shown the efficacy of γδ T cells against glioblastoma, but no previous studies have identified the ligand–receptor interactions between γδ T cells and glioblastoma cells. Here, we identify those ligand–receptor interactions and provide a basis for using γδ T cells to treat glioblastoma. Vγ9Vδ2 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 γδ 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 γδ T cells varied among the PDG cells. IFN-γ and Granzyme B secretion levels were significantly higher when γδ 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 γδ T cell–mediated cytotoxicity and cytokine secretion. Intratumoral injection of γδ T cells showed anti-tumor effects in an orthotopic mouse model. Allogenic γδ 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 γδ T cells for glioblastoma treatment.
Databáze: Directory of Open Access Journals
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