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Research Article
Mendelian randomization analysis of the causal association between immune cells and pancreatic cancer
1 Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, No. 253 Mid Gongye Ave, Haizhu District, Guangzhou, Guangdong Province, Postal code 510282, China
2 Department of Radiation Oncology, Luang Me Hospital of University of Health Sciences, Street 271, Phnom Penh, Postal code 120110, Cambodia
Address correspondence to:
Duanyu Wang
and Jiqiang Li
Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, No. 253 Mid Gongye Ave, Haizhu District, Guangzhou, Guangdong Province, Postal code 510282,
China
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Article ID: 100019G01PN2025
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Nov P, Touch S, Sou S, Kouy S, Wang D, Li J. Mendelian randomization analysis of the causal association between immune cells and pancreatic cancer. Edorium J Gastroenterol 2025;10(1):1–10.ABSTRACT
Aims: Pancreatic cancer (PC) is a highly lethal malignancy with limited treatment options. Tumor-infiltrating immune cells have been implicated in the progression and prognosis of PC. However, the causal role of immune cell populations in pancreatic cancer development and progression remains unclear. This study aims to elucidate the causal relationships between specific immune cell populations and the risk of pancreatic cancer, addressing gaps in current understanding.
Method: We conducted an extensive two-sample Mendelian randomization (MR) analysis. Using publicly available genetic data, we investigated the causal relationship between 731 immune cells and PC. We used inverse variance weighting (IVW) and weighted medians for MR analyses and used sensitivity analyses to assess heterogeneity and pleiotropy.
Results: In terms of the association between immune cells and PC, we found that CD62L- HLA DR++ monocyte % monocytes (OR = 1.1081, 95% CI = 1.0175–1.2068, p = 0.0184), SSC–A on HLA DR+ CD8br (OR = 1.1068, 95% CI = 1.0024-1.2221, p = 0.0448), CD64 on monocytes (OR = 0.8594, 95% CI = 0.8021-0.9207, p < 0.001), double-negative (DN) (CD4-CD8-) NKT %T cells (OR = 0.8712, 95% CI = 0.7802-0.9728, p = 0.0143), and SSC–A on HLA DR+ CD4+ cells (OR = 0.8902, 95% CI = 0.8028-0.9870, p = 0.0272) were strongly associated with PC. Among them, CD62L- HLA DR++ monocyte % monocytes and SSC–A on HLA DR+ CD8br are the risk factors, while CD64 on monocytes, DN (CD4-CD8-) NKT %T cells, and SSC–A on HLA DR+ CD4+ cells are protective factors for PC.
Conclusion: Our analysis provides evidence for a causal relationship between specific immune cell populations and PC. Targeting immune cell populations with therapeutic interventions such as immunotherapies may hold promise for improving outcomes in PC patients. Further studies are warranted to validate these findings and explore the underlying mechanisms involved in the immune response to PC.
Keywords: Genome wide association study (GWAS), Immune cells, Mendelian randomization (MR), Pancreatic cancer
SUPPORTING INFORMATION
Author Contributions
Pengkhun Nov - Substantial contributions to conception and design, Acquisition of data, Analysis of data, Interpretation of data, Revising it critically for important intellectual content, Final approval of the version to be published
Socheat Touch - Substantial contributions to conception and design, Acquisition of data, Analysis of data, Interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Syphanna Sou - Substantial contributions to conception and design, Analysis of data, Interpretation of data, Revising it critically for important intellectual content, Final approval of the version to be published
Samnang Kouy - Interpretation of data, Drafting the article, Final approval of the version to be published
Duanyu Wang - Interpretation of data, Drafting the article, Final approval of the version to be published
Jiqiang Li - Substantial contributions to conception and design, Revising it critically for important intellectual content, Final approval of the version to be published
Guarantor of SubmissionThe corresponding author is the guarantor of submission.
Source of SupportNone
Consent StatementWritten informed consent was obtained from the patient for publication of this article.
Data AvailabilityAll relevant data are within the paper and its Supporting Information files.
Conflict of InterestAuthors declare no conflict of interest.
Copyright© 2025 Pengkhun Nov et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.
