Crizotinib-induced immunogenic cell death in non-small cell lung cancer
Crizotinib-induced immunogenic cell death in non-small cell lung cancer
复制标题
克唑替尼诱导的非小细胞肺癌免疫原性细胞死亡
DOI：
10.1038/s41467-019-09415-3
复制
发表时间：
2019-04-02
影响因子：
16.6
通讯作者：
Kroemer, Guido
中科院分区：
文献类型：
--
作者：
Liu, Peng;Zhao, Liwei;Kroemer, Guido
Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10 mu M) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-y neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.
