5-Aza-2′-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy

Malgorzata Wachowska, Magdalena Gabrysiak, Angelika Muchowicz, Weronika Bednarek, Joanna Barankiewicz, Tomasz Rygiel, Louis Boon, Pawel Mroz, Michael R. Hamblin, Jakub Golab

Research output: Contribution to journalArticle

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Abstract

Photodynamic therapy (PDT) of tumours is based on administration of a photosensitiser followed by irradiation of the tumour with visible light leading to production of reactive oxygen species that cause direct tumour cell death and vascular damage. PDT also initiates acute local inflammation, which facilitates the development of adaptive antitumour immunity. It has recently been reported that PDT can induce strong antitumour immunity towards tumours cells expressing P1A, tumour-associated antigen. Using four different tumour models, we show that antitumour immune response can be further improved when PDT is combined with a clinically approved epigenetic agent that induces expression of a silenced P1A antigen. Induction of P1A with 5-aza-2′-deoxycytidine, a methyltransferase inhibitor, resulted in potentiated antitumour effects in mice with Lewis lung carcinoma and 4T1 mammary carcinoma when combined with PDT treatment. In CT26 colon carcinoma and EMT6 mammary carcinoma models the combination therapy resulted in complete responses and long-term survival. All long-term surviving mice were resistant to re-inoculation with the same tumour cells. Antitumour efficacy of the combination treatment was severely impaired by depletion of CD8+ cytotoxic T cells, whereas adoptive transfer of CD8+ T cells from long-term surviving mice allowed for significant tumour growth delay in tumour-bearing mice. Taken together, these findings show that PDT leads to strong specific antitumour immune responses, and that epigenetic modification of tumour antigens levels may be a novel approach to further enhance the effectiveness of PDT. The present results provide a strong rationale for clinical development of this therapeutic approach.

Original languageEnglish (US)
Pages (from-to)1370-1381
Number of pages12
JournalEuropean Journal of Cancer
Volume50
Issue number7
DOIs
StatePublished - Jan 1 2014

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decitabine
Photochemotherapy
Neoplasms
Neoplasm Antigens
Epigenomics
Breast Neoplasms
Lewis Lung Carcinoma
T-Lymphocytes
Photosensitizing Agents
Adoptive Transfer
Methyltransferases
Adaptive Immunity

Keywords

  • 5-Aza-2′-deoxycitidine
  • Cancer
  • Photodynamic therapy
  • Specific antitumour immunity
  • Tumour associated antigens

Cite this

Wachowska, M., Gabrysiak, M., Muchowicz, A., Bednarek, W., Barankiewicz, J., Rygiel, T., ... Golab, J. (2014). 5-Aza-2′-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy. European Journal of Cancer, 50(7), 1370-1381. https://doi.org/10.1016/j.ejca.2014.01.017

5-Aza-2′-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy. / Wachowska, Malgorzata; Gabrysiak, Magdalena; Muchowicz, Angelika; Bednarek, Weronika; Barankiewicz, Joanna; Rygiel, Tomasz; Boon, Louis; Mroz, Pawel; Hamblin, Michael R.; Golab, Jakub.

In: European Journal of Cancer, Vol. 50, No. 7, 01.01.2014, p. 1370-1381.

Research output: Contribution to journalArticle

Wachowska, M, Gabrysiak, M, Muchowicz, A, Bednarek, W, Barankiewicz, J, Rygiel, T, Boon, L, Mroz, P, Hamblin, MR & Golab, J 2014, '5-Aza-2′-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy', European Journal of Cancer, vol. 50, no. 7, pp. 1370-1381. https://doi.org/10.1016/j.ejca.2014.01.017
Wachowska M, Gabrysiak M, Muchowicz A, Bednarek W, Barankiewicz J, Rygiel T et al. 5-Aza-2′-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy. European Journal of Cancer. 2014 Jan 1;50(7):1370-1381. https://doi.org/10.1016/j.ejca.2014.01.017
Wachowska, Malgorzata ; Gabrysiak, Magdalena ; Muchowicz, Angelika ; Bednarek, Weronika ; Barankiewicz, Joanna ; Rygiel, Tomasz ; Boon, Louis ; Mroz, Pawel ; Hamblin, Michael R. ; Golab, Jakub. / 5-Aza-2′-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy. In: European Journal of Cancer. 2014 ; Vol. 50, No. 7. pp. 1370-1381.
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