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Human Sodium/Iodide Symporter-Mediated Radioiodine Gene Therapy Enhances the Killing Activities of CTLs in a Mouse Tumor Model

Cited 4 time in Web of Science Cited 4 time in Scopus
Authors
Jeon, Yong Hyun; Choi, Yun; Kim, Chul Woo; Kim, Young-Hwa; Lee, Jaetae; Chung, June-Key; Youn, Hyewon
Issue Date
2010-01
Publisher
AMER ASSOC CANCER RESEARCH
Citation
MOLECULAR CANCER THERAPEUTICS; Vol.9 1; 126-133
Abstract
We examined whether human sodium/iodide symporter (hNIS) radioiodine gene therapy can modulate the phenotype of cancer cells and enhance the killing activities of CTLs in a mouse tumor model. Various doses of I-131 (75, 300, 600, 1,200, and 2,400 mu Ci/5 mL) were incubated with hNIS-expressing colon cancer (CT26/hNIS) and parental cells (CT26), and numbers of MHC class I and Fas-expressing cells were determined by fluorescence-activated cell sorting (FACS). In addition, CT26/ hNIS or CT26 tumor-bearing mice were treated with 1,200 mu Ci of I-131, and percentages of MHC class I and Fas-expressing tumor cells were determined by FACS. The levels of tumor-infiltrating CD8+IFN gamma+ and CD11c+CD86+ cells and CTL killing activities were measured in CT26/ hNIS tumor-bearing mice (treated with PBS or 1,200 mu Ci of I-131) by FACS and lactate dehydrogenase assay, respectively. MHC class I and Fas gene expressions were markedly upregulated in CT26/ hNIS cells, but not in CT26 cells, in an I-131 dose-dependent manner. The level of MHC class I and Fas-expressing cancer cell were 4.5-fold and 2.1-fold higher in CT26/ hNIS tumors than in CT26 tumors, respectively (P < 0.01). Interestingly, numbers of tumor-infiltrating CD8+IFN gamma+ cells and CD11c+CD86+ cells were 5-fold and 2.5-fold higher in I-131-treated tumors than in PBS tumors, respectively (P < 0.001). Furthermore, CTL assays showed significantly more specific tumor cell lysis in I-131 tumors than in PBS tumors (P < 0.01). Our findings suggest that hNIS radioiodine gene therapy can generate tumor-associated immunity in tumor microenvironments and enhance the killing activities of CTLs. Mol Cancer Ther; 9(1); 126-33. (C) 2010 AACR.
ISSN
1535-7163
Language
English
URI
https://hdl.handle.net/10371/76694
DOI
https://doi.org/10.1158/1535-7163.MCT-09-0540
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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