Photodynamic therapy of murine mastocytoma induces specific immune responses against the cancer/testis antigen P1A.
Photodynamic therapy (PDT) involves the intravenous administration of photosensitizers followed by illumination of the tumor with visible light, leading to local production of reactive oxygen species that cause vascular shutdown and tumor cell death. Antitumor immunity is stimulated after PDT because of the acute inflammatory response that involves activation of the innate immune system, leading to stimulation of adaptive immunity. We carried out PDT using benzoporphyrin derivative and 690-nm light after 15 minutes, in DBA/2 mice bearing either the mastocytoma, P815, which expresses the naturally occurring cancer/testis antigen P1A, or the corresponding tumor P1.204 that lacks P1A expression. Tumor cures, significantly higher survival, and rejection of tumor rechallenge were obtained with P815, which were not seen with P1.204 or seen with P815 growing in nude mice. Both CD4 and CD8 T cells had higher levels of intracellular cytokines when isolated from mice receiving PDT of P815 tumors than P1.204 tumors and CD8 T cells from P815-cured mice recognized the peptide epitope of the P1A antigen (LPYLGWLVF) using pentamer staining. Taken together, these findings show that PDT can induce a potent antigen- and epitope-specific immune response against a naturally occurring mouse tumor antigen.
Authors' Affiliations: Wellman Center for Photomedicine, Massachusetts General Hospital; Department of Dermatology, Harvard Medical School, Boston; Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts; and Department of Immunology, Medical University of Warsaw, Warsaw, Poland.
Pawel
P
Mroz
Fatma
F
Vatansever
Angelika
A
Muchowicz
Michael R
MR
Hamblin
D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D008027:Light; D034801:Mastocytoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D010778:Photochemotherapy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; C076546:tumor rejection antigen P815A, mouse