| Literature DB >> 35122000 |
Jiang Liu1,2,3, Liyan Lao1,2, Jianing Chen1,2,3, Jiang Li1,2, Wenfeng Zeng1,2, Xiaofeng Zhu1,2, Jiaqian Li1,2, Xueman Chen1,2, Linbin Yang1,2,3, Yue Xing1,2, Fei Chen1,2, Di Huang1,2,3, Xiaoqian Zhang1,2, Wei Wei4, Chang Gong1,2,3, Shuya Huang5,6, Zhigang Yu5,6, Zhihua Li7, Linhan Yang8, Jinping Liu8, Xiaozhen Liu9, Qinghui Zheng10, Xuli Meng10, Jing Liang11, Luyang Sun11, Musheng Zeng12, Mengfeng Li13, Qiang Liu1,2,3, Shicheng Su14,15,16,17, Erwei Song18,19,20,21,22.
Abstract
Although chemotherapy can stimulate antitumor immunity by inducing interferon (IFN) response, the functional role of tumor-associated macrophages in this scenario remains unclear. Here, we found that IFN-activated proinflammatory macrophages after neoadjuvant chemotherapy enhanced antitumor immunity but promoted cancer chemoresistance. Mechanistically, IFN induced expression of cytoplasmic long noncoding RNA IFN-responsive nuclear factor-κB activator (IRENA) in macrophages, which triggered nuclear factor-κB signaling via dimerizing protein kinase R and subsequently increased production of protumor inflammatory cytokines. By constructing macrophage-conditional IRENA-knockout mice, we found that targeting IRENA in IFN-activated macrophages abrogated their protumor effects, while retaining their capacity to enhance antitumor immunity. Clinically, IRENA expression in post-chemotherapy macrophages was associated with poor patient survival. These findings indicate that lncRNA can determine the dichotomy of inflammatory cells on cancer progression and antitumor immunity and suggest that targeting IRENA is an effective therapeutic strategy to reversing tumor-promoting inflammation.Entities:
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Year: 2021 PMID： 35122000 DOI： 10.1038/s43018-021-00196-7
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347