Hydroxychloroquine can impair tumor response to anti-PD1 in subcutaneous mouse models.
Hydroxychloroquine can impair tumor response to anti-PD1 in subcutaneous mouse models.
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DOI：
10.1016/j.isci.2020.101990
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发表时间：
2021-01-22
期刊：
影响因子：
5.8
通讯作者：
Greten TF
中科院分区：
文献类型：
--
作者：
Wabitsch S;McVey JC;Ma C;Ruf B;Kamenyeva O;McCallen JD;Diggs LP;Heinrich B;Greten TF
羟氯喹（HCQ）是一种众所周知的抗炎药，但也被称为抗炎药。在这里，我们评估HCQ治疗对抗PD 1肿瘤免疫治疗效果的影响。使用抗PD 1治疗敏感的肿瘤细胞系MC 38、CT 26和RIL-175来研究HCQ对抗PD 1治疗功效的影响。体外试验表明，HCQ直接抑制所有测试的肿瘤细胞系中的肿瘤细胞生长。HCQ处理在体外和体内均损害抗原特异性和非特异性T细胞产生TNFα和IFNγ。重要的是，在所有三种肿瘤模型中，HCQ治疗显著损害了对抗PD 1治疗的应答，伴随着体内T细胞活化减少和肿瘤浸润性抗原特异性CD 8 + T细胞减少。这项研究表明，HCQ治疗可导致免疫治疗失败，这是由于其免疫抑制作用抵消了肿瘤细胞增加的MHC-I表达和直接的细胞毒性。HCQ抑制抗原特异性和非特异性CD 4+和CD 8 + T细胞功能HCQ抑制肿瘤细胞体外生长HCQ损害抗PD 1治疗癌症;免疫学
Hydroxychloroquine (HCQ) is a well-known anti-inflammatory drug but is also known as an anti-inflammatory drug. Here, we evaluate the influence of HCQ treatment on the effect of anti-PD1 tumor immunotherapy. Anti-PD1 therapy-sensitive tumor lines MC38, CT26, and RIL-175 were used to investigate the impact of HCQ on anti-PD1 therapy efficacy. In vitro assays demonstrated that HCQ directly inhibited tumor cell growth in all the tested tumor cell lines. HCQ treatment impaired both antigen-specific and nonspecific T-cell production of TNFα and IFNγ in vitro and in vivo. Importantly, in all the three tumor models, HCQ treatment significantly impaired the response to anti-PD1 treatment, accompanying diminished in vivo T-cell activation and reduced tumor-infiltrating, antigen-specific CD8+ T cells. This study shows that HCQ treatment can result in immunotherapy failure due to its immunosuppressive effects that offset both increased MHC-I expression by tumor cell and direct cytotoxicity. HCQ inhibits both antigen-specific and nonspecific CD4+ and CD8+ T function HCQ inhibits tumor cell growth in vitro HCQ impairs anti-PD1 therapy Cancer; Immunology
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影响因子：
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作者：
Rizvi S;Fischbach SR;Bronk SF;Hirsova P;Krishnan A;Dhanasekaran R;Smadbeck JB;Smoot RL;Vasmatzis G;Gores GJ
通讯作者：
Gores GJ
影响因子：
24.3
作者：
Guan, Wei-jie;Liang, Wen-hua;He, Jian-xing
通讯作者：
He, Jian-xing
影响因子：
--
作者：
Briceno, Eduardo;Calderon, Alejandra;Sotelo, Julio
通讯作者：
Sotelo, Julio
DOI：
10.1007/s00262-018-2190-4
发表时间：
2018-08
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Brown ZJ;Yu SJ;Heinrich B;Ma C;Fu Q;Sandhu M;Agdashian D;Zhang Q;Korangy F;Greten TF
通讯作者：
Greten TF
羟氯喹通过增强化疗敏化和促进 M2-TAM 向 M1 样巨噬细胞的转变来诱导肺癌抑制。
DOI：
10.1186/s13046-018-0938-5
发表时间：
2018-10-29
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Li Y;Cao F;Li M;Li P;Yu Y;Xiang L;Xu T;Lei J;Tai YY;Zhu J;Yang B;Jiang Y;Zhang X;Duo L;Chen P;Yu X
通讯作者：
Yu X