Increased expression of ICAM-1 and sensitivity to NK cell cytotoxicity of human cancer cells by ionizing radiation
Jae-Uk Jung1, Uong Nguyen Thanh Tung 2,3, Chanh Tin Pham2,3, Sang-Ki Kim4, Dong-Jun Shin2,4, Mee Sun Yoon1*
1Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea
2Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeollanam-do, Korea
3Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, Korea
4Department of Companion & Laboratory Animal Science, Kongju National University, Yesan, Korea
Purpose: Natural killer (NK) cells adhere to target cells through the interaction between NK cell receptors, lymphocyte function-associated antigen 1 (LFA-1), and their ligands, endothelial intercellular adhesion molecule-1 (ICAM-1), within the immunological synapse and activate signals for lytic granule polarization in NK cells. Irradiation induces increased expression of ICAM-1 on target cells. However, the contribution of enhanced expression of ICAM-1 by irradiation for NK cell cytotoxicity is unclear. The purpose of our investigation was to evaluate the effect of expression of ICAM-1 in cancer cells by irradiation and the correlation with cytotoxicity of NK cells.
Methods and Materials: Expression level of ICAM-1 on the target cell surface before and after irradiation of 5 human cancer cell lines (HL-60, SK-BR-3, HCT-116, U937, and U251) were analyzed using flow cytometry. Cytotoxicity of NK cells was analyzed by calcein-acetoxymethyl assay.
Results: The expression of ICAM-1 was induced by irradiation after 24 hours in various cell lines including HL-60, SK-BR-3, HCT-116, and U937, although the level of expression was various depending on cell lines. In a cell line of HL-60, ICAM-1 was expressed more than 3 times compared to non-irradiated cancer cells. Enhanced expression of ICAM-1 was followed by increased susceptibilities to NK cell-mediated cytotoxicity.
Conclusion: Irradiation upregulate the expression of ICAM-1 on surface of cancer cell. This triggers enhanced NK cell adhesion by LFA-1 to ICAM-1 and activating NK cell cytotoxicity. Our data demonstrate a direct effect of overexpressed ICAM-1 of irradiated human cancer cells on the cytotoxicity of NK cells.
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