Intravenous injection of the oncolytic virus M1 awakens antitumor T cells and overcomes resistance to checkpoint blockade.
Intravenous injection of the oncolytic virus M1 awakens antitumor T cells and overcomes resistance to checkpoint blockade.
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静脉注射溶瘤病毒M1唤醒抗肿瘤T细胞并克服对检查点封锁的抵抗力
DOI：
10.1038/s41419-020-03285-0
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发表时间：
2020-12-12
影响因子：
9
通讯作者：
Liang J
中科院分区：
文献类型：
--
作者：
Liu Y;Cai J;Liu W;Lin Y;Guo L;Liu X;Qin Z;Xu C;Zhang Y;Su X;Deng K;Yan G;Liang J
逆转高度免疫抑制的肿瘤微环境（TME）对于癌症免疫疗法实现长期疗效至关重要。尽管在多种类型的癌症中对检查点阻断的临床反应令人印象深刻，但只有少数患者受益于这种方法。在这里，我们报告说，溶瘤病毒M1诱导免疫原性肿瘤细胞死亡，随后恢复树突状细胞的能力，以总理抗肿瘤T细胞。静脉注射M1破坏了特权TME中的免疫耐受，将免疫沉默（冷）肿瘤重编程为免疫炎症（热）肿瘤。M1在免疫原性差的肿瘤模型中发挥强效的CD 8 + T细胞依赖性治疗作用，并建立长期抗肿瘤免疫记忆。M1预处理通过促进T细胞募集和上调PD-L1表达，使难治性肿瘤对随后的检查点阻断敏感。这些发现揭示了M1病毒的抗肿瘤免疫机制，并表明溶瘤病毒是检查点阻断免疫治疗的理想联合治疗。
Reversing the highly immunosuppressive tumor microenvironment (TME) is essential to achieve long-term efficacy with cancer immunotherapy. Despite the impressive clinical response to checkpoint blockade in multiple types of cancer, only a minority of patients benefit from this approach. Here, we report that the oncolytic virus M1 induces immunogenic tumor cell death and subsequently restores the ability of dendritic cells to prime antitumor T cells. Intravenous injection of M1 disrupts immune tolerance in the privileged TME, reprogramming immune-silent (cold) tumors into immune-inflamed (hot) tumors. M1 elicits potent CD8+ T cell-dependent therapeutic effects and establishes long-term antitumor immune memory in poorly immunogenic tumor models. Pretreatment with M1 sensitizes refractory tumors to subsequent checkpoint blockade by boosting T-cell recruitment and upregulating the expression of PD-L1. These findings reveal the antitumor immunological mechanism of the M1 virus and indicated that oncolytic viruses are ideal cotreatments for checkpoint blockade immunotherapy.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
50.3
作者：
Hellmann MD;Callahan MK;Awad MM;Calvo E;Ascierto PA;Atmaca A;Rizvi NA;Hirsch FR;Selvaggi G;Szustakowski JD;Sasson A;Golhar R;Vitazka P;Chang H;Geese WJ;Antonia SJ
通讯作者：
Antonia SJ
影响因子：
10.3
作者：
Ito, Hideaki;Aoki, Hiroshi;Kondo, Seiji
通讯作者：
Kondo, Seiji
影响因子：
20.4
作者：
Grote, Hans Juergen;Feng, Zheng;Kerr, Keith M.
通讯作者：
Kerr, Keith M.
DOI：
10.1056/nejmoa1801946
发表时间：
2018-05-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hellmann MD;Ciuleanu TE;Pluzanski A;Lee JS;Otterson GA;Audigier-Valette C;Minenza E;Linardou H;Burgers S;Salman P;Borghaei H;Ramalingam SS;Brahmer J;Reck M;O'Byrne KJ;Geese WJ;Green G;Chang H;Szustakowski J;Bhagavatheeswaran P;Healey D;Fu Y;Nathan F;Paz-Ares L
通讯作者：
Paz-Ares L