title: The effect of photodynamic therapy on tumor cell expression of major histocompatibility complex (MHC) class I and MHC class I-related molecules.
abstract: OBJECTIVE
  Photodynamic therapy (PDT) is FDA-approved anti-cancer modality for elimination of early disease and palliation in advanced disease. PDT efficacy depends in part on elicitation of a tumor-specific immune response that is dependent on cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. The cytolytic potential of CTLs and NK cells is mediated by the ability of these cells to recognize major histocompatibility complex (MHC) class I and MHC class I-related molecules. The MHC class I-related molecules MICA and MICB are induced by oxidative stress and have been reported to activate NK cells and co-stimulate CD8(+) T cells. The purpose of this study was to examine the effect of PDT on tumor cell expression of MHC classes I and II-related molecules in vivo and in vitro.
  
  
  METHODS
  Human colon carcinoma Colo205 cells and murine CT26 tumors were treated with 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH)-PDT at various doses. MHC classes I and I-related molecule expression following treatment of Colo205 cells was temporally examined by flow cytometry using antibodies specific for components of MHC class I molecules and by quantitative PCR using specific primers. Expression of MHC class I-related molecules following HPPH-based PDT (HPPH-PDT) of murine tumors was monitored using a chimeric NKG2D receptor.
  
  
  RESULTS
  In vitro HPPH-PDT significantly induces MICA in Colo205 cells, but had no effect on MHC class I molecule expression. PDT also induced expression of NKG2D ligands (NKG2DL) following in vivo HPPH-PDT of a murine tumor. Induction of MICA corresponded to increased NK killing of PDT-treated tumor cells.
  
  
  CONCLUSIONS
  PDT induction of MICA on human tumor cells and increased expression of NKG2DL by murine tumors following PDT may play a role in PDT induction of anti-tumor immunity. This conclusion is supported by our results demonstrating that tumor cells have increased sensitivity to NK cell lysis following PDT.
authors.affiliation: Department of Immunology, Elm and Carlton Sts., Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Belicha-Villanueva
authors.forename: Jonah
authors.initials: J
authors.lastname: Riddell
authors.forename: Naveen
authors.initials: N
authors.lastname: Bangia
authors.forename: Sandra O
authors.initials: SO
authors.lastname: Gollnick
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods*; D012313:RNA / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
chemical_list: D015395:Histocompatibility Antigens Class I; D012313:RNA