Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression
Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression
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DOI：
10.1038/nm0598-581
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发表时间：
1998-05-01
期刊：
影响因子：
82.9
通讯作者：
Vile, RG
中科院分区：
文献类型：
--
作者：
Melcher, A;Todryk, S;Vile, RG
通过非凋亡途径使用自杀基因转移原位杀伤肿瘤细胞，与高免疫原性和诱导热休克蛋白（hsp）表达相关。相比之下，一种主要被细胞凋亡杀死的同基因结直肠癌细胞系CMT93表现出低水平的热休克蛋白表达和较低的免疫原性。当过量表达bcl-2抑制CMT93细胞凋亡时，hsp也被诱导。此外，当编码hsp70的cDNA稳定转染到B16和CMT93细胞时，其表达显著增强了两种肿瘤的免疫原性。非凋亡细胞杀伤诱导的热休克蛋白水平升高，可能在体内提供免疫刺激信号，帮助打破对肿瘤抗原的耐受性。这些发现对于开发旨在促进患者对自身肿瘤的免疫反应的新型抗癌疗法具有重要意义。
In situ killing of tumor cells using suicide gene transfer to generate death by a non-apoptotic pathway was associated with high immunogenicity and induction of heat shock protein (hsp) expression. In contrast, a syngeneic colorectal tumor line, CMT93, killed predominantly by apoptosis, showed low levels of hsp expression and less immunogenicity. When apoptosis was inhibited in CMT93 cells by overexpression of bcl-2, hsp was also induced. Furthermore, when cDNA encoding hsp70 was stably transfected into B16 and CMT93 cells, its expression significantly enhanced the immunogenicity of both tumors. Increased levels of hsp, induced by non-apoptotic cell killing, may provide an immunostimulatory signal in vivo which helps break tolerance to tumor antigens. These findings have important implications for the development of novel anti-cancer therapies aimed at promoting patients' immune responses to their own tumors.