Induction of anti-tumor CD8 T cell responses by experimental ECP-induced human dendritic antigen presenting cells.
Extracorporeal photochemotherapy (ECP), or photopheresis, is distinguished by the specificity of the clinically potent immunologic reactions it initiates or regulates. The selectivity of ECP-induced immunoprotection for the malignant clone in cutaneous T cell lymphoma (CTCL), and for the pathogenic clones in allograft rejection and graft-versus-host disease (GVHD), has suggested a central mechanistic role for dendritic antigen presenting cells (DC). Discovery of ECP's induction of monocyte-derived DC, via monocyte signaling by ECP-plate activated platelets, and the absolute dependency of experimental ECP on such induced DC, supports that premise. Herein, we show that ECP-induced DC are capable of stimulating CD8 T cell responses to tumor antigens with which they are loaded. They internalize an antigen-specific melanoma-associated protein then present it onto a class I major histocompatibility, which then stimulates expansion of anti-tumor CD8 T cell populations. We conclude that ECP-induced DC prominently contribute to its initiation of anti-tumor immunity and raise the possibility that the therapy may be applicable to the immunotherapeutic management of a broader spectrum of cancers.
Department of Dermatology, Yale University, New Haven, CT 06520.
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Kibbi
Department of Dermatology, Yale University, New Haven, CT 06520.
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Sobolev
Department of Dermatology, Yale University, New Haven, CT 06520.
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Girardi
Department of Dermatology, Yale University, New Haven, CT 06520. Electronic address: redelson@yale.edu.
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Edelson
D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000628:therapy; D008545:Melanoma / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D017893:Photopheresis
D000951:Antigens, Neoplasm
Antigen-presenting cell (APC); CD8 T cell proliferation; Extracorporeal photochemotherapy; Melanoma antigen recognized by T cells-1 (MART-1)