Abstract
Photodynamic therapy (PDT)-generated cancer vaccine represents an attractive potential application of PDT, therapeutic modality destroying targeted lesions by localized photooxidative stress. Since immunoregulatory cell activity has become recognized as a major obstacle to effective cancer immunotherapy, the present study examined their participation in the therapeutic effect of PDT cancer vaccine. Following protocols from previous studies, mouse with squamous cell carcinoma SCCVII tumors were vaccinated by SCCVII cells treated by PDT and response monitored by tumor size measurement. The effects of low-dose cyclophosphamide (50 mg/kg) and all-trans retinoic acid (ATRA) on the numbers of Tregs and myeloid-derived suppressor cells (MDSCs) were determined by antibody staining followed by flow cytometry, while their impact on PDT vaccine therapy was evaluated by monitoring changes in tumor responses. Cyclophosphamide effectively reduced the numbers of Tregs, which became elevated following PDT vaccine treatment, and this resulted in an increase in the vaccine’s effectiveness. A similar benefit for the therapy outcome with PDT vaccine was attained by ATRA treatment. The activities of Tregs and MDSCs thus have a critical impact on therapy outcome with PDT vaccine and reducing their numbers substantially improves the vaccine’s effectiveness.
Highlights
Development of photodynamic therapy (PDT)-generated cancer vaccines [1,2] remains one of the attractive potential applications of PDT, a clinically established modality for the destruction of tumors or other lesions through localized formation of cytotoxic reactive oxygen species by light-activated drugs [3,4]
Low-dose cyclophosphamide has a pronounced effect on the therapeutic efficacy of PDT vaccines
The growth of SCCVII tumors that was significantly delayed following the administration of PDT vaccine was further retarded by injecting the host mice with cyclophosphamide (CY) (50 mg/kg i.p.), and this effect was pronounced with giving the drug at either three or one days before vaccination, or one day after vaccination (Figure 1)
Summary
Development of photodynamic therapy (PDT)-generated cancer vaccines [1,2] remains one of the attractive potential applications of PDT, a clinically established modality for the destruction of tumors or other lesions through localized formation of cytotoxic reactive oxygen species by light-activated drugs (photosensitizers) [3,4]. It was shown that a selective depletion of regulatory T cells (Tregs) by low-dose cyclophosphamide administration improves the therapeutic efficacy of PDT in attaining cures of treated tumors.
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