Publication details

CMV-Independent Lysis of Glioblastoma by Ex Vivo Expanded/Activated Vdelta1+ gamma-delta T Cells


KNIGHT Andrea ARNOUK Hilal BRITT William GILLESPIE G. Yancey CLOOUD Gretchen A. HARKINS Lualhati SU Yun LOWDELL Mark W. LAMB Lawrence S.

Year of publication 2013
Type Article in Periodical
Magazine / Source PLoS One
Field Oncology and hematology
Description Vdelta2(neg) gamma-delta T cells, of which Vdelta1+ gamma-delta T cells are by far the largest subset, are important effectors against CMV infection. Malignant gliomas often contain CMV genetic material and proteins, and evidence exists that CMV infection may be associated with initiation and/or progression of glioblastoma multiforme (GBM). We sought to determine if Vdelta1+ gamma-delta T cells were cytotoxic to GBM and the extent to which their cytotoxicity was CMV dependent. We examined the cytotoxic effect of ex vivo expanded/activated Vdelta1+ gamma-delta T cells from healthy CMV seropositive and CMV seronegative donors on unmanipulated and CMV-infected established GBM cell lines and cell lines developed from short- term culture of primary tumors. Expanded/activated Vdelta1+ T cells killed CMV-negative U251, U87, and U373 GBM cell lines and two primary tumor explants regardless of the serologic status of the donor. Experimental CMV infection did not increase Vdelta1+ T cell - mediated cytotoxicity and in some cases the cell lines were more resistant to lysis when infected with CMV. Flow cytometry analysis of CMV-infected cell lines revealed down-regulation of the NKG2D ligands ULBP-2, and ULBP-3 as well as MICA/B in CMV-infected cells. These studies show that ex vivo expanded/activated Vdelta1+ gamma-delta T cells readily recognize and kill established GBM cell lines and primary tumor-derived GBM cells regardless of whether CMV infection is present, however, CMV may enhance the resistance GBM cell lines to innate recognition possibly contributing to the poor immunogenicity of GBM.

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