Romidepsin (FK228) regulates the expression of the immune checkpoint ligand PD-L1 and suppresses cellular immune functions in colon cancer.
Romidepsin (FK228) regulates the expression of the immune checkpoint ligand PD-L1 and suppresses cellular immune functions in colon cancer.
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罗米地辛 (FK228) 调节免疫检查点配体 PD-L1 的表达并抑制结肠癌中的细胞免疫功能
DOI：
10.1007/s00262-020-02653-1
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Shi Y;Fu Y;Zhang X;Zhao G;Yao Y;Guo Y;Ma G;Bai S;Li H
罗米地辛（FK 228）是一种组蛋白去乙酰化酶抑制剂（HDACi），对几种类型的实体瘤具有抗肿瘤作用。研究表明，HDACi可以上调肿瘤细胞中PD-L1的表达，并改变体内抗肿瘤免疫反应的状态。然而，罗米地辛诱导的肿瘤细胞中PD-L1表达增强对抗肿瘤免疫应答的影响仍在争论中。因此，本研究旨在探讨罗米地辛对结肠癌的抗肿瘤作用及其对免疫反应的影响。结果表明，罗米地辛抑制CT 26和MC 38细胞增殖，诱导G 0/G1细胞周期阻滞，并增加凋亡。罗米地辛处理通过增加组蛋白H3和H4的乙酰化水平和调节转录因子BRD 4来增加体内和体外PD-L1表达。在皮下移植瘤小鼠和结肠炎相关癌（CAC）小鼠中，罗米地辛增加外周血和肿瘤微环境中FOXP 3+调节性T细胞（TCRs）的百分比，降低Th 1/Th 2细胞的比率和IFN-γ+ CD 8 + T细胞的百分比。在与抗PD-1抗体组合后，罗米地辛的抗肿瘤作用增强，并且对CD 4+和CD 8 + T细胞的影响部分逆转。因此，罗米地辛与抗PD-1免疫疗法的联合为结肠癌提供了更有潜力的治疗方法。
Romidepsin (FK228), a histone deacetylase inhibitor (HDACi), has anti-tumor effects against several types of solid tumors. Studies have suggested that HDACi could upregulate PD-L1 expression in tumor cells and change the state of anti-tumor immune responses in vivo. However, the influence of enhanced PD-L1 expression in tumor cells induced by romidepsin on anti-tumor immune responses is still under debate. So, the purpose of this study was to explore the anti-tumor effects and influence on immune responses of romidepsin in colon cancer. The results indicated that romidepsin inhibited proliferation, induced G0/G1 cell cycle arrest and increased apoptosis in CT26 and MC38 cells. Romidepsin treatment increased PD-L1 expression in vivo and in vitro via increasing the acetylation levels of histones H3 and H4 and regulating the transcription factor BRD4. In subcutaneous transplant tumor mice and colitis-associated cancer (CAC) mice, romidepsin increased the percentage of FOXP3+ regulatory T cells (Tregs), decreased the ratio of Th1/Th2 cells and the percentage of IFN-γ+ CD8+ T cells in the peripheral blood and the tumor microenvironment. Upon combination with an anti-PD-1 antibody, the anti-tumor effects of romidepsin were enhanced and the influence on CD4+ and CD8+ T cells was partially reversed. Therefore, the combination of romidepsin and anti-PD-1 immunotherapy provides a more potential treatment for colon cancer.
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影响因子：
5.7
作者：
Halaburková A;Jendželovský R;Kovaľ J;Herceg Z;Fedoročko P;Ghantous A
通讯作者：
Ghantous A
影响因子：
7.2
作者：
Riganti, Chiara;Lingua, Marcello Francesco;Taulli, Riccardo
通讯作者：
Taulli, Riccardo
影响因子：
5.8
作者：
Briere, David;Sudhakar, Niranjan;Christensen, James G.
通讯作者：
Christensen, James G.
影响因子：
4.8
作者：
Hu, Xiangming;Lu, Xiaodong;Chen, Ruichuan
通讯作者：
Chen, Ruichuan
PD-1，PD-1配体的关联以及肿瘤免疫微环境的其他特征与抗PD-1治疗的响应。
DOI：
10.1158/1078-0432.ccr-13-3271
发表时间：
2014-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Taube JM;Klein A;Brahmer JR;Xu H;Pan X;Kim JH;Chen L;Pardoll DM;Topalian SL;Anders RA
通讯作者：
Anders RA