Evidence map›Paper›PMID 40591041›Full record

ArticleDiscover oncology2025

Causal relationships between immune-related adverse events, immune cell characteristics, and plasma metabolites: insights from Mendelian randomization study.

Zhiyuan Shi, Zhao Sun, Dingding Zhang, Lin Zhao

Abstract read
In one paragraph

Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

4 authors.

Zhiyuan ShiDepartment of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China.
Zhao SunDepartment of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China.
Dingding ZhangCenter for Prevention and Early Intervention, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan,Wangfujing, Dongcheng District, Beijing, 100730, China. dingdingzh1987@163.com.
Lin ZhaoDepartment of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China. zhaolin4412@pumch.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe severe adverse events of immunotherapy have limited its clinical application. Immune cell characteristics and plasma metabolites are probably associated with immune-related adverse events, but current studies have not combined the three dynamically. This study is designed to analyze causality between immune cell characteristics and immune-related adverse events, and the degree to which plasma metabolites mediate it.

methodsData were obtained from genome-wide association studies. Initially, we conducted a two-sample bidirectional Mendelian randomization analysis to assess causal links between immune cell characteristics and immune-related adverse events. Following that, a two-step Mendelian randomization approach was utilized to measure the proportion of total effects mediated by 1400 plasma metabolites. Additionally, sensitivity analyses were conducted at each step to reduce horizontal pleiotropy and heterogeneity.

resultsWe identified 12 immune cell characteristics, and 31 plasma metabolites causally associated with immune-related adverse events. Through mediation effect analysis, 6 immune cell characteristics (CD4 on monocyte,CM CD4 + AC, EM CD4 + %T cell, CD39 + CD4 + AC, HLA DR on CD14 + CD16 + monocyte, CD45RA on TD CD8br) were identified as being correlated with the presence of immune-related adverse events, which were partially mediated by 5 metabolic characteristics (Ornithine to phosphate ratio, 1-palmitoyl-GPE (16:0) levels, 5-hydroxyhexanoate levels, (2,4 or 2,5)-dimethylphenol sulfate levels, 2-palmitoleoyl-GPC (16:1) levels). Among them, 2-palmitoleoyl-GPC (16:1) levels demonstrated the most significant mediating effect, mediating 10.8% (p = 0.0155) of the effect of CD45RA on TD CD8br on immune-related adverse events. The mediating effect is derived through a two-step MR analysis.

conclusionsWe identified genetic causality among the characteristics of immune cells, plasma metabolites, and immune-related adverse events. By regulating immune cells and plasma metabolites through various methods, it may be possible to alleviate immune-related adverse events. This discovery serves as a valuable reference for the judicious application of immunotherapy in future endeavors.

Indexed as

Immune cellsImmune-related adverse eventsMediation effectsMendelian randomizationPalmitoylationPlasma metabolites

Identifiers

PMID40591041
PMCPMC12214199

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.