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首页> 外文期刊>The journal of clinical investigation >Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance
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Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance

机译：触发人类肺癌细胞表达的TLR7和TLR8诱导细胞存活和化学抗性

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Compelling evidence suggests that inflammation, cell survival, and cancer are linked, with a central role played by NF-κB. Recent studies implicate some TLRs in tumor development based on their ability to facilitate tumor growth; however, to our knowledge, involvement of neither TLR7 nor TLR78 has yet been demonstrated. Here we have demonstrated expression of TLR7 and TLR8, the natural receptors for single-stranded RNA, by tumor cells in human lung cancer in situ and in human lung tumor cell lines. Stimulation with TLR7 or TLR8 agonists led to activated NF-κB, upregulated expression of the antiapoptotic protein Bcl-2, increased tumor cell survival, and chemoresistance. Transcriptional analysis performed on human primary lung tumor cells and TLR7- or TLR8-stimulated human lung tumor cell lines revealed a gene expression signature suggestive of chronic stimulation of tumor cells by TLR ligands in situ. Together, these data emphasize that TLR signaling can directly favor tumor development and further suggest that researchers developing anticancer immunotherapy using TLR7 or TLR8 agonists as adjuvants should take into account the expression of these TLRs in lung tumor cells.
机译：有力的证据表明，炎症，细胞存活和癌症与NF-κB发挥重要作用有关。最近的研究基于其促进肿瘤生长的能力将一些TLR暗示为肿瘤发展。但是，据我们所知，尚未证明TLR7和TLR78的参与。在这里，我们已经证明了人肺癌原位和人肺肿瘤细胞系中肿瘤细胞对TLR7和TLR8（单链RNA的天然受体）的表达。用TLR7或TLR8激动剂刺激可激活NF-κB，上调抗凋亡蛋白Bcl-2的表达，增加肿瘤细胞存活率和化学抗性。对人原发性肺肿瘤细胞和TLR7或TLR8刺激的人肺肿瘤细胞系进行的转录分析显示，基因表达特征提示TLR配体可长期刺激肿瘤细胞。总之，这些数据强调了TLR信号传导可以直接促进肿瘤的发展，并进一步建议开发使用TLR7或TLR8激动剂作为佐剂的抗癌免疫疗法的研究人员应考虑这些TLR在肺肿瘤细胞中的表达。

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