Unraveling the causal role of immune cells in gastrointestinal tract cancers - insights from a Mendelian randomization study

Sep 21, 2026

Despite early research, the relationship between immune characteristics and gastrointestinal tract cancers remains incompletely defined, limiting the identification of actionable immunotherapeutic targets. This study applies two-sample Mendelian randomization to evaluate causal effects of 731 immune traits across esophageal, gastric, small intestine, colon, and rectal cancers. Results identify 78 immune traits linked to disease risk and 60 immune traits associated with protection, supported by sensitivity analyses for robustness, heterogeneity, and horizontal pleiotropy. The findings clarify site-specific causal immune mechanisms and suggest new directions for prevention and therapy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Background

Methods

Results

Conclusion

Key findings

Causal immune traits across cancer sites

Protective immune traits

Introduction

TYPE Original Research PUBLISHED 12 March 2024 DOI 10.3389/fimmu.2024.1343512 OPEN ACCESS EDITED BY Qun Zhao, Fourth Hospital of Hebei Medical University, China REVIEWED BY Kui Wang, Shanghai Jiao Tong University, China Mubashir Ayaz Ahmed, AMITA Health St Joseph Hospital, United States *CORRESPONDENCE Ya-ming Zhang [zhangyaming2014@163.com](zhangyaming2014@163.com)[ ](zhangyaming2014@163.com)Yao Wang [wangyaodna@foxmail.com](wangyaodna@foxmail.com) RECEIVED 23 November 2023 ACCEPTED 21 February 2024 PUBLISHED 12 March 2024 CITATION Wang Y-x, Zhou C-p, Wang D-t, Ma J, Sun X-h, Wang Y and Zhang Y-m (2024) Unraveling the causal role of immune cells in gastrointestinal tract cancers: insights from a Mendelian randomization study. Front. Immunol. 15:1343512 . doi: 10.3389/fimmu.2024.1343512 COPYRIGHT © 2024 Wang, Zhou, Wang, Ma, Sun, Wang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Unraveling the causal role of immune cells in gastrointestinal tract cancers: insights from a Mendelian randomization study Yu-xiang Wang 1, Chao-ping Zhou 1, Da-tian Wang 1, Jun Ma 1, Xue-hu Sun 2, Yao Wang 3* and Ya-ming Zhang 1* 1 Department of General Surgery, Anqing Municipal Hospital, Anqing, Anhui, China, 2 Department of Emergency Surgery, The First Afﬁliated Hospital of Anhui Medical University, Hefei, Anhui, China, 3 Department of Digestive Endoscopy, The First Afﬁliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China Background: Despite early attempts, the relationship between immune characteristics and gastrointestinal tract cancers remains incompletely elucidated. Hence, rigorous and further investigations in this domain hold signiﬁcant clinical relevance for the development of novel potential immunotherapeutic targets. Methods: We conducted a two-sample Mendelian randomization (MR) analysis using the tools available in the “TwoSampleMR” R package. The GWAS data for these 731 immune traits were sourced from the GWAS Catalog database. Concurrently, data on gastrointestinal tract cancers, encompassing malignant tumors in the esophagus, stomach, small intestine, colon, and rectum, were extracted from the FinnGen database. The immune traits subjected to MR analysis predominantly fall into four categories: median ﬂuorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP) . To ensure the reliability of our ﬁndings, sensitivity analyses were implemented to address robustness, account for heterogeneity, and alleviate the impact of horizontal pleiotropy. Results: A total of 78 immune traits causally linked to gastrointestinal tract cancers were identiﬁed, encompassing esophageal cancer (12 traits), gastric cancer (13 traits), small intestine cancer (22 traits), colon cancer (12 traits), and rectal cancer (19 traits) . Additionally, 60 immune traits were recognized as protective factors associated with gastrointestinal tract cancers, distributed across esophageal cancer (14 traits), gastric cancer (16 traits), small intestine cancer (7 traits), colon cancer (14 traits), and rectal cancer (9 traits) . Furthermore, it was observed that seven immune traits are causally related to gastrointestinal tract cancers in at least two locations. These traits include “CCR2 on CD14-CD16+ monocyte,” “CD19 on IgD+ CD38-,” “CD19 on IgD+ CD38- naive,” “CD25hi CD45RA+ CD4 not Treg AC,” “CD27 on unsw mem,” “CD28 on CD39+ activated Treg,” and “CD45 on CD4+ .” Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Conclusion: This study eluci

FAQs

What is the main purpose of this study?

To clarify causal relationships between immune cells and gastrointestinal tract cancers using genetic evidence from Mendelian randomization.

How were the immune traits and cancer outcome data obtained?

Immune traits came from GWAS Catalog (731 immune traits), while gastrointestinal tract cancer outcomes covering multiple sites were extracted from FinnGen.

How many immune traits were found to be causally linked to these cancers?

The study identified 78 immune traits causally associated with gastrointestinal tract cancers and 60 immune traits as protective factors.

Sep 21, 2026

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