Tanshinone IIA enhances susceptibility of non‐small cell lung cancer cells to NK cell‐mediated lysis by up‐regulating ULBP1 and DR5
Tanshinone IIA enhances susceptibility of non‐small cell lung cancer cells to NK cell‐mediated lysis by up‐regulating ULBP1 and DR5
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丹参酮 IIA 通过上调 ULBP1 和 DR5 增强非小细胞肺癌细胞对 NK 细胞介导的裂解的敏感性
DOI：
10.1002/jlb.5ma1120-776rr
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发表时间：
2021-04
影响因子：
5.5
通讯作者：
Shiguo Zhu
中科院分区：
文献类型：
--
作者：
Yufang Sun;Chenyuan Gong;Zhongya Ni;Dan Hu;Wanyi Ng;Xiaowen Zhu;Lixin Wang;Guifan Si;Xuewei Yan;Chen Zhao;Chao Yao;Shiguo Zhu
自然杀伤细胞在肿瘤免疫治疗中具有巨大的潜力。然而，由于癌细胞的免疫逃逸，其治疗效果在临床上受到限制。因此，迫切需要开发新的方法来提高NK细胞的抗肿瘤免疫能力。本研究发现，天然产物丹参酮IIA （TIIA）可增强NK细胞介导的非小细胞肺癌（NSCLC）细胞的杀伤作用。在免疫功能不全的小鼠模型中，TIIA联合NK细胞过继性转移协同抑制非小细胞肺癌细胞的肿瘤生长。此外，在具有免疫能力的同基因小鼠模型中，TIIA显著抑制Lewis肺癌（LLC）的肿瘤生长，这种抑制作用被NK细胞的消耗逆转。此外，TIIA增加了NSCLC细胞中ULBP1和DR5的表达，抑制DR5和ULBP1降低了TIIA对NK细胞介导的裂解的增强。此外，TIIA增加了p - PERK、ATF4和CHOP的水平。在所有检测到的NSCLC细胞中，敲低ATF4完全逆转了TIIA对ULBP1和DR5的上调，而敲低CHOP仅在小部分NSCLC细胞中部分降低了这些增强的表达。这些结果表明，TIIA可以通过上调ULBP1和DR5来增加NSCLC细胞对NK细胞介导的裂解的敏感性，这表明TIIA在癌症免疫治疗中具有很好的潜力，特别是在基于NK细胞的癌症免疫治疗中。
Natural killer (NK) cells have a great potential in cancer immunotherapy. However, their therapeutic efficacy is clinically limited owing to cancer cell immune escape. Therefore, it is urgently necessary to develop novel method to improve the antitumor immunity of NK cells. In the present study, it was found that the natural product tanshinone IIA (TIIA) enhanced NK cell‐mediated killing of non‐small cell lung cancer (NSCLC) cells. TIIA in combination with adoptive transfer of NK cells synergistically suppressed the tumor growth of NSCLC cells in an immune‐incompetent mouse model. Furthermore, TIIA significantly inhibited the tumor growth of Lewis lung cancer (LLC) in an immune‐competent syngeneic mouse model, and such inhibitory effect was reversed by the depletion of NK cells. Moreover, TIIA increased expressions of ULBP1 and DR5 in NSCLC cells, and inhibition of DR5 and ULBP1 reduced the enhancement of NK cell‐mediated lysis by TIIA. Besides, TIIA increased the levels of p‐PERK, ATF4 and CHOP. Knockdown of ATF4 completely reversed the up‐regulation of ULBP1 and DR5 by TIIA in all detected NSCLC cells, while knockdown of CHOP only partly reduced these enhanced expressions in small parts of NSCLC cells. These results demonstrated that TIIA could increase the susceptibility of NSCLC cells to NK cell‐mediated lysis by up‐regulating ULBP1 and DR5, suggesting that TIIA had a promising potential in cancer immunotherapy, especially in NK cell‐based cancer immunotherapy.
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影响因子：
7.3
作者：
Carrega P;Ferlazzo G
通讯作者：
Ferlazzo G
罗卡酰胺通过抑制自噬增强 NK 细胞介导的非小细胞肺癌细胞杀伤作用
影响因子：
13.3
作者：
Yao, Chao;Ni, Zhongya;Zhu, Shiguo
通讯作者：
Zhu, Shiguo
影响因子：
2.3
作者：
Yi Zhang;Ren-xiong Wei;Xiaobao Zhu;Lin Cai;Wei Jin;Hao Hu
通讯作者：
Yi Zhang;Ren-xiong Wei;Xiaobao Zhu;Lin Cai;Wei Jin;Hao Hu
影响因子：
2.9
作者：
Xian Zhang;Yong Zhou;Y. Gu
通讯作者：
Xian Zhang;Yong Zhou;Y. Gu
影响因子：
10.1
作者：
S. Terry;Abdérémane Abdou;A. Engelsen;Stéphanie Buart;P. Dessen;Stéphanie Corgnac;D. Collares;G. Meurice;G. Gausdal;V. Baud;P. Saintigny;J. Lorens;J. Thiery;F. Mami-Chouaib;S. Chouaib
通讯作者：
S. Terry;Abdérémane Abdou;A. Engelsen;Stéphanie Buart;P. Dessen;Stéphanie Corgnac;D. Collares;G. Meurice;G. Gausdal;V. Baud;P. Saintigny;J. Lorens;J. Thiery;F. Mami-Chouaib;S. Chouaib