Evidence map›Paper›PMID 38331868›Full record

ArticleCell death & disease2024

Blockade of C5aR1 resets M1 via gut microbiota-mediated PFKM stabilization in a TLR5-dependent manner.

Jie Zhao, Chen Yao, Yongqin Qin, Hanyong Zhu, Hui Guo, Binbin Ji, Xueqin Li, Na Sun, Rongqing Li, Yuzhang Wu and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026
    Review
  4. Article
  5. Article
  6. The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
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

14 authors at 2 institutions in 1 country.

Jie Zhao *Jiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Chen Yao *Jiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yongqin Qin *Jiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Hanyong ZhuJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Hui GuoJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Binbin JiJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Xueqin LiJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Na SunJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Rongqing LiJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yuzhang WuChongqing International Institute for Immunology, Chongqing, China.
Kuiyang ZhengJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China. zky@xzhmu.edu.cn.
Yuchen PanJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China. panyuchen@xzhmu.edu.cn.
Tingting ZhaoChongqing International Institute for Immunology, Chongqing, China. zhaotingting95@163.com.
Jing YangJiangsu International Laboratory of Immunity and Metabolism, Jiangsu Province Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China. jingyang@xzhmu.edu.cn.ORCID 0000-0002-2624-5028
Xuzhou Medical College · CNSichuan International Studies University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeting C5aR1 modulates the function of infiltrated immune cells including tumor-associated macrophages (TAMs). The gut microbiome plays a pivotal role in colorectal cancer (CRC) tumorigenesis and development through TAM education. However, whether and how the gut flora is involved in C5aR1 inhibition-mediated TAMs remains unclear. Therefore, in this study, genetic deletion of C5ar1 or pharmacological inhibition of C5aR1 with anti-C5aR1 Ab or PMX-53 in the presence or absence of deletion Abs were utilized to verify if and how C5aR1 inhibition regulated TAMs polarization via affecting gut microbiota composition. We found that the therapeutic effects of C5aR1 inhibition on CRC benefited from programming of TAMs toward M1 polarization via driving AKT2-mediated 6-phosphofructokinase muscle type (PFKM) stabilization in a TLR5-dependent manner. Of note, in the further study, we found that C5aR1 inhibition elevated the concentration of serum IL-22 and the mRNA levels of its downstream target genes encoded antimicrobial peptides (AMPs), leading to gut microbiota modulation and flagellin releasement, which contributed to M1 polarization. Our data revealed that high levels of C5aR1 in TAMs predicted poor prognosis. In summary, our study suggested that C5aR1 inhibition reduced CRC growth via resetting M1 by AKT2 activation-mediated PFKM stabilization in a TLR5-dependent manner, which relied on IL-22-regulated gut flora.

Indexed as

Gastrointestinal MicrobiomeMacrophagesMusclesPhosphofructokinase-1PhosphofructokinasesToll-Like Receptor 5Tumor MicroenvironmentPhosphofructokinase-1PhosphofructokinasesToll-Like Receptor 5

Identifiers

PMID38331868
PMCPMC10853248
OpenAlexW4391654315

What OpenQuestion holds

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LicenceCC BY
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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.