Evidence map›Paper›PMID 39349845›Full record

ArticleThe EMBO journal2024

Cancer cell-intrinsic biosynthesis of itaconate promotes tumor immunogenicity.

Zining Wang, Lei Cui, Yanxun Lin, Bitao Huo, Hongxia Zhang, Chunyuan Xie, Huanling Zhang, Yongxiang Liu, Huan Jin, Hui Guo and 6 more

Abstract read
In one paragraph

Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Reprogramming immunity with itaconate: metabolic mechanisms and therapeutic perspectives.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  9. Review
  10. Review
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Zining Wang *State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.ORCID http://orcid.org/0000-0002-0087-2453
Lei Cui *State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Yanxun LinState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Bitao HuoState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Hongxia ZhangState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Chunyuan XieState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.ORCID http://orcid.org/0000-0002-9906-3081
Huanling ZhangState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Yongxiang LiuState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Huan JinState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Hui GuoState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Mengyun LiState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Xiaojuan WangState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Penghui ZhouState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.ORCID http://orcid.org/0000-0003-0519-461X
Peng HuangState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.ORCID http://orcid.org/0000-0002-2152-9152
Jinyun LiuState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.ORCID http://orcid.org/0000-0002-4763-2684
Xiaojun XiaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. xiaxj@sysucc.org.cn.ORCID http://orcid.org/0000-0003-4444-7472

Funding

MOST | National Key Research and Development Program of China (NKPs) 2021YFC2400600/2021YFC2400601MOST | National Natural Science Foundation of China (NSFC) 81972692MOST | National Natural Science Foundation of China (NSFC) 82073140MOST | National Natural Science Foundation of China (NSFC) 82273189
6 · The paper itself

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.

Indexed as

Carboxy-LyasesSuccinatesAnimalsCell Line, TumorHumansHydro-LyasesMiceMice, Inbred C57BLSignal TransductionTumor MicroenvironmentACOD1 protein, humanAcod1 protein, mouseCarboxy-LyasesHydro-Lyasesitaconic acidSuccinatesImmunogenicityImmunotherapyItaconateThimerosal

Identifiers

PMID39349845
PMCPMC11574104

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.