Identification of the receptor of oncolytic virus M1 as a therapeutic predictor for multiple solid tumors.
Identification of the receptor of oncolytic virus M1 as a therapeutic predictor for multiple solid tumors.
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溶瘤病毒M1受体的鉴定作为多种实体瘤的治疗预测因子
DOI：
10.1038/s41392-022-00921-3
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发表时间：
2022-04-08
影响因子：
39.3
通讯作者：
Cai J
中科院分区：
文献类型：
--
作者：
Song D;Jia X;Liu X;Hu L;Lin K;Xiao T;Qiao Y;Zhang J;Dan J;Wong C;Hu C;Sai K;Gong S;Sander M;Shen R;Chen X;Xiao X;Chen J;Zhang Y;Wei C;Xiao X;Liang J;Zhang Q;Hu J;Zhu W;Yan G;Lin Y;Cai J
在过去的十年中，溶瘤病毒（OV）治疗在肿瘤治疗中显示出其有前途的潜力。并非每个患者都能从中受益的事实突出了定义有助于预测患者反应的生物标志物的重要性。作为一种特殊的自放大生物治疗药物，OV的抗肿瘤作用高度依赖于病毒感染和复制的宿主因素。通过加权基因共表达网络分析（WGCNA）发现基质重塑相关蛋白8（MXRA 8）与溶瘤病毒M1（OVM）诱导的溶瘤作用呈正相关。因此，MXRA 8在体外和体内促进OVM的溶瘤功效。此外，通过单粒子冷冻电子显微镜（cryo-EM）研究的MXRA 8和OVM的相互作用表明，MXRA 8直接与该病毒结合。因此，MXRA 8充当OVM的进入受体。泛癌分析显示，MXRA 8在大多数实体瘤中是丰富的，并且与邻近的正常组织相比，在肿瘤组织中是高表达的。在癌细胞系和患者来源的肿瘤组织中的进一步研究表明，OVM的肿瘤选择性主要由细胞膜受体MXRA 8和细胞内因子锌指抗病毒蛋白（ZAP）的组合作用决定。总之，我们的研究可能为OVM治疗中的精准医学提供一种新的双生物标志物。
Over the last decade, oncolytic virus (OV) therapy has shown its promising potential in tumor treatment. The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients’ responses. As particular self-amplifying biotherapeutics, the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication. By using weighted gene co-expression network analysis (WGCNA), we found matrix remodeling associated 8 (MXRA8) is positively correlated with the oncolysis induced by oncolytic virus M1 (OVM). Consistently, MXRA8 promotes the oncolytic efficacy of OVM in vitro and in vivo. Moreover, the interaction of MXRA8 and OVM studied by single-particle cryo-electron microscopy (cryo-EM) showed that MXRA8 directly binds to this virus. Therefore, MXRA8 acts as the entry receptor of OVM. Pan-cancer analysis showed that MXRA8 is abundant in most solid tumors and is highly expressed in tumor tissues compared with adjacent normal ones. Further study in cancer cell lines and patient-derived tumor tissues revealed that the tumor selectivity of OVM is predominantly determined by a combinational effect of the cell membrane receptor MXRA8 and the intracellular factor, zinc-finger antiviral protein (ZAP). Taken together, our study may provide a novel dual-biomarker for precision medicine in OVM therapy.
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影响因子：
64.5
作者：
Basore, Katherine;Kim, Arthur S.;Fremont, Daved H.
通讯作者：
Fremont, Daved H.
影响因子：
46.9
作者：
通讯作者：
--
异病毒在头颈癌细胞系中发挥有效的溶瘤作用，这与EGFR途径中的信号无关。
影响因子：
3.8
作者：
Twigger K;Roulstone V;Kyula J;Karapanagiotou EM;Syrigos KN;Morgan R;White C;Bhide S;Nuovo G;Coffey M;Thompson B;Jebar A;Errington F;Melcher AA;Vile RG;Pandha HS;Harrington KJ
通讯作者：
Harrington KJ
影响因子：
--
作者：
Hastie E;Cataldi M;Moerdyk-Schauwecker MJ;Felt SA;Steuerwald N;Grdzelishvili VZ
通讯作者：
Grdzelishvili VZ
Bcl-xL 的选择性拮抗作用通过增强线粒体凋亡来增强 M1 溶瘤作用。
影响因子：
4.2
作者：
Tan, Yaqian;Lin, Yuan;Zhang, Haipeng
通讯作者：
Zhang, Haipeng