http://scholars.ntou.edu.tw/handle/123456789/3738
Title: | LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade | Authors: | Sheng, Wanqiang LaFleur, Martin W. Nguyen, Thao H. Chen, Sujun Chakravarthy, Ankur Conway, Jake Ryan Li, Ying Chen, Hao Yang, Henry Hsu, Pang-Hung Van Allen, Eliezer M. Freeman, Gordon J. De Carvalho, Daniel D. He, Housheng Hansen Sharpe, Arlene H. Shi, Yang |
Keywords: | ENDOGENOUS RETROVIRUSES;DNA METHYLATION;CANCER-CELLS;T-CELLS;PD-1;THERAPY;TUMORS;IMMUNOTHERAPY;DEMETHYLATION;SENSITIVITY | Issue Date: | 26-Jul-2018 | Publisher: | CELL PRESS | Journal Volume: | 174 | Journal Issue: | 3 | Start page/Pages: | 549-+ | Source: | CELL | Abstract: | Chromatin regulators play a broad role in regulating gene expression and, when gone awry, can lead to cancer. Here, we demonstrate that ablation of the histone demethylase LSD1 in cancer cells increases repetitive element expression, including endogenous retroviral elements (ERVs), and decreases expression of RNA-induced silencing complex (RISC) components. Significantly, this leads to double-stranded RNA (dsRNA) stress and activation of type 1 interferon, which stimulates anti-tumor T cell immunity and restrains tumor growth. Furthermore, LSD1 depletion enhances tumor immunogenicity and T cell infiltration in poorly immunogenic tumors and elicits significant responses of checkpoint blockade-refractory mouse melanoma to anti-PD-1 therapy. Consistently, TCGA data analysis shows an inverse correlation between LSD1 expression and CD8(+) T cell infiltration in various human cancers. Our study identifies LSD1 as a potent inhibitor of antitumor immunity and responsiveness to immunotherapy and suggests LSD1 inhibition combined with PD-(L)1 blockade as a novel cancer treatment strategy. |
URI: | http://scholars.ntou.edu.tw/handle/123456789/3738 | ISSN: | 0092-8674 | DOI: | 10.1016/j.cell.2018.05.052 |
Appears in Collections: | 海洋生物科技學士學位學程(系) 生命科學暨生物科技學系 03 GOOD HEALTH AND WELL-BEING |
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