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

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

Author information

1
1] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA [2] Department of Dermatology, Medical University of Graz, Graz 8036, Austria.

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.

PMID:
24064977
PMCID:
PMC3798975
DOI:
10.1038/bjc.2013.580
[Indexed for MEDLINE]
Free PMC Article

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