Immune Cell Profiles and Novel Insights Into Cancer Risk: A Focus on Oral and Pharyngeal Cancer.

Authors

Xin Deng, Shaohong Huang

Published in

Human mutation. Volume 2026. Pages 6585175. Epub Jul 09, 2026.

Abstract

Oral and pharyngeal cancers affect 850,000 new cases annually with 440,000 deaths worldwide. This study explores the causal relationship between immune cell profiles and oral-pharyngeal cancer risk through Mendelian randomization analysis integrated with experimental validation.
A two-sample Mendelian randomization study was conducted using the MRC IEU OpenGWAS platform, analyzing data from 3757 European individuals for immune cell profiles and 4671 oral-pharyngeal cancer cases, with 80% statistical power to detect OR ≥ 1.2. Multiple Mendelian randomization methods were employed, including inverse-variance weighted, MR-Egger, and weighted median approaches. Findings were validated through coculture experiments examining immune cell-cancer cell interactions via flow cytometry.
Among 731 immune traits analyzed, Mendelian randomization revealed elevated cancer risk associated with CD127 on CD45RA+ CD4+ T cells (OR = 1.33, 95% CI: 1.04-1.70, p = 0.025, F - statistic = 53.08), CD4 on CD39+ CD4+ T cells (OR = 1.17, 95% CI: 1.01-1.35, p = 0.032, F = 34.88), and HLA-DR on CD8+ T cells (OR = 1.25, 95% CI: 1.04-1.50, p = 0.018, F = 50.99). Flow cytometry validation (n = 3 independent experiments, five replicates each) demonstrated that memory B cells enhanced cancer cell viability (92.95% ± 3.2% at 72 h, p < 0.001) while inhibiting apoptosis. Conversely, naive CD8+ T cells showed antitumor effects, reducing cancer cell viability to 67.99% ± 2.8% and inducing apoptosis (28.42% ± 1.9% vs. 12.35% ± 1.2% control, p < 0.001).
This integrated analysis not only reveals novel immune cell-cancer risk associations and their underlying mechanisms but also provides promising opportunities for personalized immunotherapy development in oral-pharyngeal cancer. These findings enable precise patient stratification based on immune cell profiles and suggest tailored therapeutic strategies that could significantly improve clinical outcomes.

PMID:
42428247
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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