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Role of the Immune System in Mediating the Antitumor Effect of Benzophenothiazine Photodynamic Therapy
Author(s) -
HendrzakHenion Jill A.,
Knisely Terrence L.,
Cincotta Louis,
Cincotta Eric,
Cincotta Anthony H.
Publication year - 1999
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1999.tb03330.x
Subject(s) - photodynamic therapy , in vivo , cytotoxic t cell , cd8 , immune system , cancer research , antibody , in vitro , immunology , population , chemistry , medicine , biology , biochemistry , microbiology and biotechnology , organic chemistry , environmental health
Abstract— The role of the host immune system in contributing to tumor regression following benzophenothiazine photodynamic therapy (PDT) was examined. Photodynamic therapy with 2‐iodo‐5‐ethylamino‐9‐diethylaminobenzo[ a ]‐phenothiazinium chloride (2I‐EtNBS) eradicated EMT‐6 mammary fibrosarcomas in 75–100% of treated mice. In contrast, PDT failed to inhibit tumor growth in T‐cell‐deficient nude mice. Furthermore, T‐cell depletion studies with anti‐CD8 antibody revealed that the CD8 + T‐cell population was critical for an effective PDT response (tumor volume 14 days post‐PDT: 262 mm 3 vs 59 mm 3 in controls; P < 0.01). Because anti‐CD4 antibody inhibited tumor growth in the absence of PDT, the role of CD4 + T cells remains unclear. Depletion of natural killer (NK) cells in vivo with anti‐asialo‐GM1 antibody significantly reduced a suboptimal PDT effect relative to vehicle controls (tumor volume 13 days post‐PDT: 513 mm 3 vs 85 mm 3 respectively; P < 0.001). However, splenic NK cells obtained from PDT‐treated tumor‐bearing mice were not cytotoxic in vitro against EMT‐6 cells, suggesting that NK cells contribute to the PDT effect in vivo by an indirect mechanism. In addition, when mice with complete tumor regression following PDT were rechallenged 28 days later with 5 × 10 5 EMT‐6 cells, tumor growth was signficantly inhibited as compared to controls (tumor volume 40 days postrechallenge: 137 mm 3 vs 833 mm 3 in controls; P < 0.03; percent animals without tumor in five experiments: 67% vs 8% in controls). Collectively, these results demonstrate that CD8 + T cells are required to prevent tumor regrowth after 2I‐EtNBSPDT, NK cells contribute to this response and such PDT can elicit protective antitumor immunity.