The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing
The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing
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DOI：
10.1158/1078-0432.ccr-08-0335
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发表时间：
2008-07-01
影响因子：
11.5
通讯作者：
Hodge, James W.
中科院分区：
文献类型：
--
作者：
Chakraborty, Mala;Wansley, Elizabeth K.;Hodge, James W.
目的：将人类肿瘤细胞暴露于亚致死剂量的外部射线辐射下，上调肿瘤抗原和辅助分子的表达，使肿瘤细胞更容易被抗原特异性 CTL 杀死。这项研究探讨了暴露于姑息剂量的放射性药物可能会改变肿瘤细胞的表型，使它们更容易受到 T 细胞介导的杀伤的可能性。 实验设计：这里，10 个人类肿瘤细胞系（4 个前列腺、2 个乳腺癌和 4 个肺）暴露于剂量不断增加的放射性药物钐-153-乙二胺四亚甲基磷酸盐 (153 Sm-EDTMP)，用于治疗癌症。癌症患者治疗骨转移引起的疼痛。对前列腺癌中涉及的五种表面分子和几种肿瘤相关抗原的表达进行了荧光激活细胞分选分析和定量实时PCR分析。将 LNCaP 人前列腺癌细胞暴露于 1 53 Sm-EDTMP 中，并在 CTL 杀伤试验中与肿瘤相关抗原特异性 CTL 一起孵育，以确定暴露于 153 Sm-EDTMP 是否使 LNCaP 细胞更容易受到 T 细胞介导的杀伤。 结果：肿瘤细胞上调表面分子 Fas（100% 的细胞系上调 Fas）、癌胚抗原（90%）、mucin-1 (60%)、MHC 1 类 (50%) 和细胞间粘附分子 1 (40%) 对 153 Sm-EDTMP 的反应。实时定量 PCR 分析显示肿瘤抗原有额外上调。暴露于 153 Sm-EDTMP 使 LNCaP 细胞更容易被前列腺特异性抗原、癌胚抗原和 mucin-1 特异性的 CTL 杀死。结论：相当于姑息剂量的 153 Sm-EDTMP 递送至骨，改变了肿瘤细胞的表型，表明 1 53 Sm-EDTMP 可能与免疫疗法协同作用，以增加对肿瘤细胞的敏感性。肿瘤细胞被CTL杀伤。
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.