期刊
CLINICAL CANCER RESEARCH
卷 14, 期 13, 页码 4241-4249出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-08-0335
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资金
- Intramural NIH HHS [Z01 SC010373-08] Funding Source: Medline
Purpose: Exposing human tumor cells to sublethal doses of external beam radiation up-regulates expression of tumor antigen and accessory molecules, rendering tumor cells more susceptible to killing by antigen-specific CTLs. This study explored the possibility that exposure to palliative doses of a radiopharmaceutical agent could alter the phenotype of tumor cells to render them more susceptible to T cell - mediated killing. Experimental Design: Here, 10 human tumor cell lines (4 prostate, 2 breast, and 4 lung) were exposed to increasing doses of the radiopharmaceutical samarium-153-ethylenediaminetetramethylenephosphonate (153 Sm-EDTMP) used in cancer patients to treat pain due to bone metastasis. Flu orescence-activated cell sorting analysis and quantitative real-time PCR analysis for expression of five surface molecules and several tumor-associated antigens involved in prostate cancer were done. LNCaP human prostate cancer cells were exposed to 1 53 Sm-EDTMP and incubated with tumor-associated antigen-specific CTL in a CTL killing assay to determine whether exposure to 153 Sm-EDTMP rendered LNCaP cells more susceptible to T cell - mediated killing. Results: Tumor cells up-regulated the surface molecules Fas (100% of cell lines up-regulated Fas), carcinoembryonic antigen (90%), mucin-1 (60%), MHC class 1 (50%), and intercellular adhesion molecule-1 (40%) in response to 153 Sm-EDTMP. Quantitative real-time PCR analysis revealed additional up-regulated tumor antigens. Exposure to 153 Sm-EDTMP rendered LNCaP cells more susceptible to killing by CTLs specific for prostate-specific antigen, carcinoembryonic antigen, and mucin-1. Conclusions: Doses of 153 Sm-EDTMP equivalent to palliative doses delivered to bone alter the phenotype of tumor cells, suggesting that 1 53 Sm-EDTMP may work synergistically with immunotherapy to increase the susceptibility of tumor cells to CTL killing.
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