Photodynamic therapy plus regulatory T-cell depletion produces immunity against a mouse tumour that expresses a self-antigen

Br J Cancer. 2013 Oct 15;109(8):2167-74. doi: 10.1038/bjc.2013.580. Epub 2013 Sep 24.

Abstract

Background: Photodynamic therapy (PDT) can lead to development of antigen-specific immune response and PDT-mediated immunity can be potentiated by T regulatory cell (Treg) depletion. We investigated whether the combination of PDT with cyclophosphamide (CY) could foster immunity against wild-type tumours expressing self-antigen (gp70).

Methods: Mice with CT26 tumours were treated with PDT alone or in combination with low-dose CY. T regulatory cell numbers and transforming growth factor-β (TGF-β) levels were measured at several time points after treatment. Mice cured by PDT+CY were rechallenged with CT26 and monitored for long-term survival.

Results: Photodynamic therapy+CY led to complete tumour regression and long-term survival in 90% of treated mice while the absolute numbers of Treg decreased after PDT+CY and the TGF-β levels were reduced to a level comparable to naïve mice. Sixty-five percent of the mice treated with PDT+CY that survived over 90 days tumour free rejected the rechallenge with the same tumour when a second dose of CY was administered before rechallenge but not without.

Conclusion: Administration of CY before PDT led to depletion of Treg and potentiated PDT-mediated immunity, leading to long-term survival and development of memory immunity that was only uncovered by second Treg depletion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / immunology*
  • Autoantigens / biosynthesis
  • Autoantigens / immunology*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Combined Modality Therapy
  • Cyclophosphamide / pharmacology*
  • Immunologic Memory / drug effects
  • Immunologic Memory / immunology
  • Immunosuppressive Agents / pharmacology*
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Photochemotherapy / methods*
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / blood

Substances

  • Antigens, Neoplasm
  • Autoantigens
  • Immunosuppressive Agents
  • Transforming Growth Factor beta
  • Cyclophosphamide