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The effect of photodynamic therapy on tumor cell expression of major histocompatibility complex (MHC) class I and MHC class I-related molecules

Authors

  • Alan Belicha-Villanueva PhD,

    1. Department of Immunology, Elm and Carlton Sts., Roswell Park Cancer Institute, Buffalo, New York 14263
    2. Photodynamic Therapy Center, Elm and Carlton Sts., Roswell Park Cancer Institute, Buffalo, New York 14263
    Current affiliation:
    1. Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
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  • Jonah Riddell BS,

    1. Photodynamic Therapy Center, Elm and Carlton Sts., Roswell Park Cancer Institute, Buffalo, New York 14263
    2. Department of Cell Stress Biology, Elm and Carlton Sts., Roswell Park Cancer Institute, Buffalo, New York 14263
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  • Naveen Bangia PhD,

    1. Department of Immunology, Elm and Carlton Sts., Roswell Park Cancer Institute, Buffalo, New York 14263
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  • Sandra O. Gollnick PhD

    Corresponding author
    1. Photodynamic Therapy Center, Elm and Carlton Sts., Roswell Park Cancer Institute, Buffalo, New York 14263
    2. Department of Cell Stress Biology, Elm and Carlton Sts., Roswell Park Cancer Institute, Buffalo, New York 14263
    • Photodynamic Therapy Center, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263.
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  • Conflict of interest: none.

Abstract

Background and 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.

Study Design/Materials and 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. Lasers Surg. Med. 44:60–68, 2012. © 2012 Wiley Periodicals, Inc.

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