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Supplementary Table S7 from An Inflammatory Checkpoint Generated by IL1RN Splicing Offers Therapeutic Opportunity for KRAS-Mutant Intrahepatic Cholangiocarcinoma

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posted on 2023-10-05, 07:20 authored by Mao Zhang, Yingying Huang, Jiaomeng Pan, Chen Sang, Youpei Lin, Liangqing Dong, Xia Shen, Yingcheng Wu, Guohe Song, Shuyi Ji, Fen Liu, Mengcheng Wang, Yuyan Zheng, Sirui Zhang, Zefeng Wang, Jianke Ren, Daming Gao, Jian Zhou, Jia Fan, Wu Wei, Jian Lin, Qiang Gao

Supplementary Table S7. Patient information.

Funding

National Natural Science Foundation of China (NSFC)

Science and Technology Commission of Shanghai Municipality (STCSM)

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ARTICLE ABSTRACT

KRAS mutations are causally linked to protumor inflammation and are identified as driving factors in tumorigenesis. Here, using multiomics data gathered from a large set of patients, we showed that KRAS mutation was associated with a specific landscape of alternative mRNA splicing that connected to myeloid inflammation in intrahepatic cholangiocarcinoma (iCCA). Then, we identified a negative feedback mechanism in which the upregulation of interleukin 1 receptor antagonist (IL1RN)-201/203 due to alternative splicing confers vital anti-inflammatory effects in KRAS-mutant iCCA. In KRAS-mutant iCCA mice, both IL1RN-201/203 upregulation and anakinra treatment ignited a significant antitumor immune response by altering neutrophil recruitment and phenotypes. Furthermore, anakinra treatment synergistically enhanced anti–PD-1 therapy to activate intratumoral GZMB+ CD8+ T cells in KRAS-mutant iCCA mice. Clinically, we found that high IL1RN-201/203 levels in patients with KRAS-mutant iCCA were significantly associated with superior response to anti–PD-1 immunotherapy. This work describes a novel inflammatory checkpoint mediated by IL1RN alternative splicing variants that may serve as a promising basis to develop therapeutic options for KRAS-mutant iCCA and other cancers.This article is featured in Selected Articles from This Issue, p. 2109

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