Dendritic-cell-based immunotherapy evokes potent anti-tumor immune responses in CD105+ human renal cancer stem cells

Mol Carcinog. 2017 Nov;56(11):2499-2511. doi: 10.1002/mc.22697. Epub 2017 Sep 14.

Abstract

Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified "stem-like" characteristics of CD105+ cells in two human RCC cell lines: A498 and SK-RC-39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC-based immunotherapy for human RCC.

Keywords: CD105; cancer stem cells; cellular immunotherapy; dendritic cell; renal cell carcinoma.

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / therapy*
  • Cell Line, Tumor
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Endoglin / analysis
  • Endoglin / immunology*
  • Female
  • Humans
  • Immunotherapy / methods*
  • Kidney / immunology
  • Kidney / pathology
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Mice, Inbred BALB C
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology

Substances

  • Endoglin