小柯机器人

美国维克森林医学院Yong Lu和美国亚利桑那州立大学Grant McFadden共同合作近期取得重要工作进展，他们研究发现粘液瘤病毒感染的CAR-T和TCR-T细胞诱导肿瘤细胞自噬以克服原发性和获得性耐药。相关论文2022年8月25日在线发表于《癌细胞》杂志上。

研究人员测试了表达嵌合抗原受体（CAR）或T细胞受体（TCR）的粘液瘤病毒（MYXV）感染的肿瘤特异性T（T^MYXV）细胞，它们系统地将MYXV递送到实体瘤中以克服原发性耐药性。除了T细胞诱导的细胞凋亡和细胞焦亡外，CAR/TCR-T^MYXV细胞对肿瘤的根除还归因于肿瘤细胞自噬性诱导，这是一种特殊的细胞死亡类型。

从机制上讲，T细胞来源的干扰素γ（IFNγ）-蛋白激酶B（AKT）信号传导与MYXV诱导的M-T5-SKP-1-VPS34信号传导协同作用以触发强大的肿瘤细胞自噬。CAR/TCR-T^MYXV引发的自噬能有效的抑制抗原逃逸。研究人员发现了T细胞和MYXV之间意想不到的协同作用，以支持实体肿瘤细胞自噬作用，从而增强肿瘤的清除。

据了解，肿瘤特异性T细胞的细胞毒性需要肿瘤细胞与T细胞之间的接触依赖诱导经典的肿瘤细胞凋亡和焦亡。然而，这可能不会触发实体肿瘤对过继细胞治疗的充分初级反应，或防止肿瘤抗原逃逸介导的获得性耐药。

附：英文原文

Title: Induction of tumor cell autosis by myxoma virus-infected CAR-T and TCR-T cells to overcome primary and acquired resistance

Author: Ningbo Zheng, Jing Fang, Gang Xue, Ziyu Wang, Xiaoyin Li, Mengshi Zhou, Guangxu Jin, Masmudur M. Rahman, Grant McFadden, Yong Lu

Issue&Volume: 2022-08-25

Abstract: Cytotoxicity of tumor-specific T cells requires tumor cell-to-T cell contact-dependentinduction of classic tumor cell apoptosis and pyroptosis. However, this may not triggersufficient primary responses of solid tumors to adoptive cell therapy or prevent tumorantigen escape-mediated acquired resistance. Here we test myxoma virus (MYXV)-infectedtumor-specific T (TMYXV) cells expressing chimeric antigen receptor (CAR) or T cell receptor (TCR), whichsystemically deliver MYXV into solid tumors to overcome primary resistance. In additionto T cell-induced apoptosis and pyroptosis, tumor eradication by CAR/TCR-TMYXV cells is also attributed to tumor cell autosis induction, a special type of celldeath. Mechanistically, T cell-derived interferon γ (IFNγ)-protein kinase B (AKT)signaling synergizes with MYXV-induced M-T5-SKP-1-VPS34 signaling to trigger robusttumor cell autosis. CAR/TCR-TMYXV-elicited autosis functions as a type of potent bystander killing to restrain antigenescape. We uncover an unexpected synergy between T cells and MYXV to bolster solidtumor cell autosis that reinforces tumor clearance.

DOI: 10.1016/j.ccell.2022.08.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00357-9

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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