Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis.
Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis.
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调节性T细胞对肝转移瘤全身免疫和免疫治疗反应的控制。
DOI：
10.1126/sciimmunol.aba0759
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发表时间：
2020-10-02
影响因子：
24.8
通讯作者：
Bluestone JA
中科院分区：
文献类型：
--
作者：
Lee JC;Mehdizadeh S;Smith J;Young A;Mufazalov IA;Mowery CT;Daud A;Bluestone JA
当用抗PD-1免疫疗法治疗时，具有肝转移的癌症患者表现出比没有肝转移的癌症患者显著更差的结果。肝转移酶诱导的全身抗肿瘤免疫力降低的机制尚不清楚。使用双肿瘤免疫活性小鼠模型，我们发现肝脏内对肿瘤抗原存在的免疫应答导致抗肿瘤免疫的全身抑制。免疫抑制是抗原特异性的，并与协调激活的调节性T细胞（T细胞）和肿瘤内CD 11b+单核细胞的调制。功能失调的免疫状态不能通过抗PD-1单一疗法逆转，除非Treg细胞被耗尽（抗CTLA-4）或不稳定（EZH 2抑制剂）。因此，本研究为添加Treg和CD 11b+单核细胞靶向剂联合抗PD-1治疗肝转移癌症患者提供了机制理解和基本原理。
Cancer patients with liver metastasis demonstrate significantly worse outcomes than those without liver metastasis when treated with anti-PD-1 immunotherapy. The mechanism of liver metastases-induced reduction in systemic antitumor immunity is unclear. Using a dual-tumor immunocompetent mouse model, we found that the immune response to tumor antigen presence within the liver led to the systemic suppression of antitumor immunity. The immune suppression was antigen-specific and associated with the coordinated activation of regulatory T cells (Tregs) and modulation of intratumoral CD11b+ monocytes. The dysfunctional immune state could not be reversed by anti-PD-1 monotherapy unless Treg cells were depleted (anti-CTLA-4) or destabilized (EZH2 inhibitor). Thus, this study provides a mechanistic understanding and rationale for adding Treg and CD11b+ monocyte targeting agents in combination with anti-PD-1 to treat cancer patients with liver metastasis.
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影响因子：
--
作者：
Budczies J;von Winterfeld M;Klauschen F;Bockmayr M;Lennerz JK;Denkert C;Wolf T;Warth A;Dietel M;Anagnostopoulos I;Weichert W;Wittschieber D;Stenzinger A
通讯作者：
Stenzinger A
影响因子：
8.8
作者：
Holmgaard RB;Zamarin D;Li Y;Gasmi B;Munn DH;Allison JP;Merghoub T;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
24.8
作者：
Ahmadzadeh, Mojgan;Pasetto, Anna;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
DOI：
10.1073/pnas.0408197102
发表时间：
2005-01-11
影响因子：
11.1
作者：
Chen, ML;Pittet, MJ;Khazaie, K
通讯作者：
Khazaie, K
影响因子：
2.4
作者：
Brown, Zachary J.;Heinrich, Bernd;Greten, Tim F.
通讯作者：
Greten, Tim F.