Sphere-derived Prostate Cancer Stem Cells Are Resistant to γδ T Cell Cytotoxicity

Abstract

Background/aim: γδ T cells mediate cytotoxicity against prostate cancer (PCa) cells in vitro; however, the clinical efficacy of γδ T cell-targeted immunotherapy for recurrent and metastatic PCa is unsatisfactory. We hypothesized that the resistance of recurrent and metastatic PCa to γδ T cells is related to the presence of prostate cancer stem cells (PCSCs), and we examined their relationship.

Materials and methods: PCa spheres (prostaspheres) were generated from five PCa cell lines, and their susceptibility to cytotoxicity by γδ T cells was investigated. Expression of stemness-related markers was evaluated by qRT-PCR.

Results: Prostasphere-derived cancer cells were resistant to lysis by γδ T cells and expressed higher levels of several stemness markers, including CD133, NANOG, SOX2, and OCT4, than the parental PCa cell lines.

Conclusion: Ex vivo-expanded γδ T cells are not effective against PCSCs.

Keywords: CD133; NANOG; OCT4; SOX2; cancer stem cell; immunotherapy; prostasphere; prostate cancer; sphere; γδ T cell.