Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses

Cancer Lett. 2016 Apr 28;374(1):175-185. doi: 10.1016/j.canlet.2016.01.021. Epub 2016 Jan 20.

Abstract

Cancer stem cells (CSCs) are demonstrated to be usually less sensitive to conventional methods of cancer therapies, resulting in tumor relapse. It is well-known that an ideal treatment would be able to selectively target and kill CSCs, so as to avoid the tumor reversion. The aim of our present study was to evaluate the effectiveness of a dendritic cell (DC) based vaccine against CSCs in a mouse model of malignant melanoma. C57BL/6 mouse bone marrow derived DCs pulsed with a murine melanoma cell line (B16F10) or CSC lysates were used as a vaccine. Immunization of mice with CSC lysate-pulsed DCs was able to induce a significant prophylactic effect by a higher increase in lifespan and obvious depression of tumor growth in tumor bearing mice. The mice vaccinated with DCs loaded with CSC-lysate were revealed to produce specific cytotoxic responses to CSCs. The proliferation assay and cytokine (IFN-γ and IL-4) secretion of mice vaccinated with CSC lysate-pulsed DCs also showed more favorable results, when compared to those receiving B16F10 lysate-pulsed DCs. These findings suggest a potential strategy to improve the efficacy of DC-based immunotherapy of cancers.

Keywords: Cancer stem cell; Dendritic cell; Immunity; Immunotherapy; Melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • CD24 Antigen / immunology
  • Cancer Vaccines / immunology
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hyaluronan Receptors / immunology
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / pathology
  • T-Lymphocytes / immunology
  • Th1 Cells / immunology

Substances

  • Antigens, Neoplasm
  • CD24 Antigen
  • Cancer Vaccines
  • Cd24a protein, mouse
  • Cd44 protein, mouse
  • Hyaluronan Receptors