Induction of anti-tumor CD8 T cell responses by experimental ECP-induced human dendritic antigen presenting cells

Transfus Apher Sci. 2016 Aug;55(1):146-52. doi: 10.1016/j.transci.2016.06.001. Epub 2016 Jun 6.

Abstract

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.

Keywords: Antigen-presenting cell (APC); CD8 T cell proliferation; Extracorporeal photochemotherapy; Melanoma antigen recognized by T cells-1 (MART-1).

MeSH terms

  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Humans
  • Lymphoma, T-Cell, Cutaneous / immunology*
  • Lymphoma, T-Cell, Cutaneous / therapy
  • Melanoma / immunology*
  • Monocytes / immunology
  • Photopheresis*

Substances

  • Antigens, Neoplasm