Document Detail

5-Aza-2'-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy.
MedLine Citation:
PMID:  24559534     Owner:  NLM     Status:  MEDLINE    
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.
Malgorzata Wachowska; Magdalena Gabrysiak; Angelika Muchowicz; Weronika Bednarek; Joanna Barankiewicz; Tomasz Rygiel; Louis Boon; Pawel Mroz; Michael R Hamblin; Jakub Golab
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2014-02-18
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  50     ISSN:  1879-0852     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-03-31     Completed Date:  2014-05-12     Revised Date:  2014-08-19    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  1370-81     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 Elsevier Ltd. All rights reserved.
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MeSH Terms
Antigens, Neoplasm / metabolism*
Antimetabolites, Antineoplastic / pharmacology*
Azacitidine / analogs & derivatives*,  pharmacology
CD8-Positive T-Lymphocytes / immunology
Carcinoma, Lewis Lung / drug therapy*,  immunology
Cell Line, Tumor
Disease Models, Animal
Flow Cytometry
Lung Neoplasms / drug therapy*,  immunology
Mice, Inbred BALB C
Mice, Inbred C57BL
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Antimetabolites, Antineoplastic; 0/cancer-testis antigen P1A, mouse; 776B62CQ27/decitabine; M801H13NRU/Azacitidine

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