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

Masatsugu Miyashita1,2, Mako Tomogane1, Yuichi Nakamura1,2

  • 1Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.

Anticancer Research
|September 29, 2020
PubMed
Abstract

Insights

Prostate cancer stem cells (PCSCs) resist killing by gamma delta T cells. This explains why current immunotherapies are ineffective against recurrent and metastatic prostate cancer.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Stem Cell Research

Background:

  • Gamma delta T cells show promise for prostate cancer (PCa) immunotherapy.
  • Clinical outcomes for recurrent and metastatic PCa treated with γδ T cells are suboptimal.

Purpose of the Study:

  • To investigate the relationship between prostate cancer stem cells (PCSCs) and resistance to γδ T cell-mediated cytotoxicity.
  • To determine if PCSCs contribute to the limited efficacy of current immunotherapies.

Main Methods:

  • Prostate cancer spheres (prostaspheres) were generated from five PCa cell lines.
  • Susceptibility of prostaspheres to γδ T cell lysis was assessed.
  • Expression of stemness markers (CD133, NANOG, SOX2, OCT4) was quantified using qRT-PCR.

Main Results:

  • Prostasphere-derived cells exhibited resistance to γδ T cell-mediated killing.
  • Elevated expression of stemness markers (CD133, NANOG, SOX2, OCT4) was observed in PCSCs compared to parental PCa cells.

Conclusions:

  • Ex vivo-expanded γδ T cells are ineffective against prostate cancer stem cells.
  • PCSCs represent a significant barrier to successful γδ T cell-based immunotherapy for advanced prostate cancer.