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


CONCLUSIONS
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.
1] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA [2] Department of Dermatology, Medical University of Graz, Graz 8036, Austria.
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Reginato
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Mroz
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Chung
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Kawakubo
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Wolf
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Hamblin
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000494:pharmacology*; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood
D000951:Antigens, Neoplasm; D001324:Autoantigens; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D003520:Cyclophosphamide