Immunoregulatory Cell Depletion Improves the Efficacy of Photodynamic Therapy-Generated Cancer Vaccines

Int J Mol Sci. 2015 Nov 12;16(11):27005-14. doi: 10.3390/ijms161126008.

Abstract

Photodynamic therapy (PDT)-generated cancer vaccine represents an attractive potential application of PDT, therapeutic modality destroying targeted lesions by localized photooxidative stress. Since immunoregulatory cell activity has become recognized as a major obstacle to effective cancer immunotherapy, the present study examined their participation in the therapeutic effect of PDT cancer vaccine. Following protocols from previous studies, mouse with squamous cell carcinoma SCCVII tumors were vaccinated by SCCVII cells treated by PDT and response monitored by tumor size measurement. The effects of low-dose cyclophosphamide (50 mg/kg) and all-trans retinoic acid (ATRA) on the numbers of Tregs and myeloid-derived suppressor cells (MDSCs) were determined by antibody staining followed by flow cytometry, while their impact on PDT vaccine therapy was evaluated by monitoring changes in tumor responses. Cyclophosphamide effectively reduced the numbers of Tregs, which became elevated following PDT vaccine treatment, and this resulted in an increase in the vaccine's effectiveness. A similar benefit for the therapy outcome with PDT vaccine was attained by ATRA treatment. The activities of Tregs and MDSCs thus have a critical impact on therapy outcome with PDT vaccine and reducing their numbers substantially improves the vaccine's effectiveness.

Keywords: all-trans retinoic acid (ATRA); cancer vaccines; cyclophosphamide; immunoregulatory cells; photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Cancer Vaccines / immunology*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Cyclophosphamide / administration & dosage
  • Disease Models, Animal
  • Humans
  • Immunomodulation*
  • Immunotherapy* / methods
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Neoplasms / immunology*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Photochemotherapy* / methods
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Alkylating
  • Cancer Vaccines
  • Cyclophosphamide