NSC243928 Treatment Induces Anti-Tumor Immune Response in Mouse Mammary Tumor Models.
NSC243928 Treatment Induces Anti-Tumor Immune Response in Mouse Mammary Tumor Models.
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作者：
本研究使用两种不同的同基因小鼠乳腺肿瘤模型来确定小分子NSC243928对肿瘤内免疫细胞的影响。我们观察到NSC243928治疗降低了体内肿瘤负荷，并改变了两种模型中广泛的免疫细胞浸润。这些结果为进一步研究NSC243928在三阴性乳腺癌免疫肿瘤药物开发中的作用铺平了道路。NSC243928以ly6k依赖性方式诱导三阴性乳腺癌细胞死亡。NSC243928已被报道为NCI小分子文库中的抗癌药物。在同基因小鼠模型中，NSC243928作为抗癌药物治疗肿瘤生长的分子机制尚未建立。随着免疫疗法的成功，可能引发抗肿瘤免疫反应的新型抗癌药物在实体癌治疗新药的开发中备受关注。因此，我们重点研究NSC243928是否能在体内4T1和E0771乳腺肿瘤模型中引发抗肿瘤免疫应答。我们观察到NSC243928诱导4T1和E0771细胞的免疫原性细胞死亡。此外，在体内，NSC243928通过增加巡逻单核细胞、NKT细胞、B1细胞等免疫细胞和减少PMN MDSCs来增加抗肿瘤免疫应答。我们需要进一步研究NSC243928在体内诱导抗肿瘤免疫应答的确切机制，从而确定与NSC243928疗效相关的分子特征。NSC243928可能是未来乳腺癌免疫肿瘤药物开发的一个良好靶点。
This study used two different syngeneic mouse mammary tumor models to determine the effect of a small molecule NSC243928 on intra-tumoral immune cells. We observed that NSC243928 treatment reduced the tumor burden in vivo and altered the wide range of immune cell infiltration in both models. These results pave the path for further study of the role of NSC243928 in immuno-oncology drug development for triple-negative breast cancer. NSC243928 induces cell death in triple-negative breast cancer cells in a LY6K-dependent manner. NSC243928 has been reported as an anti-cancer agent in the NCI small molecule library. The molecular mechanism of NSC243928 as an anti-cancer agent in the treatment of tumor growth in the syngeneic mouse model has not been established. With the success of immunotherapies, novel anti-cancer drugs that may elicit an anti-tumor immune response are of high interest in the development of novel drugs to treat solid cancer. Thus, we focused on studying whether NSC243928 may elicit an anti-tumor immune response in the in vivo mammary tumor models of 4T1 and E0771. We observed that NSC243928 induced immunogenic cell death in 4T1 and E0771 cells. Furthermore, NSC243928 mounted an anti-tumor immune response by increasing immune cells such as patrolling monocytes, NKT cells, B1 cells, and decreasing PMN MDSCs in vivo. Further studies are required to understand the exact mechanism of NSC243928 action in inducing an anti-tumor immune response in vivo, which can be used to determine a molecular signature associated with NSC243928 efficacy. NSC243928 may be a good target for future immuno-oncology drug development for breast cancer.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
11.2
作者：
AlHossiny M;Luo L;Frazier WR;Steiner N;Gusev Y;Kallakury B;Glasgow E;Creswell K;Madhavan S;Kumar R;Upadhyay G
通讯作者：
Upadhyay G
影响因子：
9
作者：
Fucikova J;Kepp O;Kasikova L;Petroni G;Yamazaki T;Liu P;Zhao L;Spisek R;Kroemer G;Galluzzi L
通讯作者：
Galluzzi L
影响因子：
8.8
作者：
Ghaffari A;Peterson N;Khalaj K;Vitkin N;Robinson A;Francis JA;Koti M
通讯作者：
Koti M
影响因子：
7.3
作者：
通讯作者：
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