一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> EMBO Journal >>article
EMBO Journal

EMBO Journal

IF: 8.3
Download PDF

Cancer cell-intrinsic biosynthesis of itaconate promotes tumor immunogenicity

Published:1 November 2024 DOI: 10.1038/s44318-024-00217-y PMID: 39349845
Zining Wang,?Lei Cui,?Yanxun Lin,?Bitao Huo,?Hongxia Zhang,?Chunyuan Xie,?Huanling Zhang,?Yongxiang Liu,?Huan Jin,?Hui Guo,?Mengyun Li,?Xiaojuan Wang,?Penghui Zhou,?Peng Huang,?Jinyun Liu,?Xiaojun Xia

Abstract

The Krebs cycle byproduct itaconate has recently emerged as an important metabolite regulating macrophage immune functions, but its role in tumor cells remains unknown. Here, we show that increased tumor-intrinsic cis-aconitate decarboxylase (ACOD1 or CAD, encoded by immune-responsive gene 1, Irg1) expression and itaconate production promote tumor immunogenicity and anti-tumor immune responses. Furthermore, we identify thimerosal, a vaccine preservative, as a specific inducer of IRG1 expression in tumor cells but not in macrophages, thereby enhancing tumor immunogenicity. Mechanistically, thimerosal induces itaconate production through a ROS-RIPK3-IRF1 signaling axis in tumor cells. Further, increased IRG1/itaconate upregulates antigen presentation-related gene expression via promoting TFEB nuclear translocation. Intratumoral injection of thimerosal induced itaconate production, activated the tumor immune microenvironment, and inhibited tumor growth in a T cell-dependent manner. Importantly, IRG1 deficiency markedly impaired tumor response to thimerosal treatment. Furthermore, itaconate induction by thimerosal potentiates the anti-tumor efficacy of adoptive T-cell therapy and anti-PD1 therapy in a mouse lymphoma model. Hence, our findings identify a new role for tumor intrinsic IRG1/itaconate in promoting tumor immunogenicity and provide a translational means to increase immunotherapy efficacy.

Substances (14)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Glyoxylic acid monohydrate 563-96-2 C2H4O4 377 suppliers $6.00-$3326.40
Glyoxylic acid monohydrate 563-96-2 C2H4O4 377 suppliers $6.00-$3326.40
Glyoxylic acid monohydrate 563-96-2 C2H4O4 377 suppliers $6.00-$3326.40
Glyoxylic acid monohydrate 563-96-2 C2H4O4 377 suppliers $6.00-$3326.40
DIGITONIN 11024-24-1 C56H92O29 373 suppliers $32.00-$3000.00
DIGITONIN 11024-24-1 C56H92O29 373 suppliers $32.00-$3000.00
DIGITONIN 11024-24-1 C56H92O29 373 suppliers $32.00-$3000.00
DIGITONIN 11024-24-1 C56H92O29 373 suppliers $32.00-$3000.00
Butanedioic acid, methylene-, 4-octyl ester 3133-16-2 C13H22O4 109 suppliers $12.00-$2400.00
Butanedioic acid, methylene-, 4-octyl ester 3133-16-2 C13H22O4 109 suppliers $12.00-$2400.00
阿勒泰市| 恩施市| 舒城县| 嵩明县| 柳林县| 永靖县| 张家川| 高尔夫| 托里县| 卢氏县| 双城市| 丘北县| 保山市| 兴安盟| 长顺县| 灵丘县| 鱼台县| 襄汾县| 那坡县| 宽城| 庐江县| 扶绥县| 宁强县| 兴和县| 嘉鱼县| 潜江市| 衡阳市| 泰兴市| 烟台市| 兴文县| 浪卡子县| 堆龙德庆县| 东明县| 桐乡市| 醴陵市| 林西县| 石屏县| 德化县| 西乌珠穆沁旗| 上林县| 织金县|