AUTHOR=Fang Xianliu , Huang Xiaoxiao , Lu Jianhua , Su Danke 

TITLE=Causal role of immune cells in thyroid cancer: a bidirectional Mendelian randomization study

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1425873

DOI=10.3389/fimmu.2024.1425873

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>The immune system plays an important role in the development and treatment of thyroid cancer(THCA).However, the correlation between immune cells and THCA has not been systematically studied.</p></sec><sec><title>Methods</title><p>This study used a two-sample Mendelian randomization (MR) study to determine the causal relationship between immune cell characteristics and THCA. Based on a large sample of publicly available genetic data, we explored the causal relationship between 731 immune cell characteristics and THCA risk. The 731 immunophenotypes were divided into 7 groups, including B cell panel(n=190),cDC panel(n=64),Maturation stages of T cell panel(n=79),Monocyte panel(n=43),Myeloid cell panel(n=64),TBNK panel(n=124),and Treg panel(n=167). The sensitivity of the results was analyzed, and heterogeneity and horizontal pleiotropy were excluded.</p></sec><sec><title>Results</title><p>After FDR correction, the effect of immunophenotype on THCA was not statistically significant. It is worth mentioning, however, that there are some unadjusted low P-values phenotypes. The odds ratio (OR) of CD62L on monocyte on THCA risk was estimated to be 0.953 (95% CI=0.930~0.976, <italic>P</italic>=1.005×10<sup>−4</sup>),and which was estimated to be 0.975(95% CI=0.961–0.989, <italic>P</italic>=7.984×10<sup>−4</sup>) for Resting Treg%CD4 on THCA risk. Furthermore, THCA was associated with a reduced risk of 5 immunophenotype:CD25 on CD39+ CD4 on Treg (OR=0.871, 95% CI=0.812~0.935, <italic>P</italic>=1.274×10<sup>−4</sup>), activated Treg AC (OR=0.884, 95% CI=0.820~0.953, <italic>P</italic>=0.001), activated &amp; resting Treg % CD4 Treg (OR=0.872, 95%CI=0.811~0.937,<italic>P</italic>=2.109×10<sup>−4</sup>),CD28- CD25++ CD8br AC(OR=0.867,95% CI=0.809~0.930,<italic>P</italic>=6.09×10<sup>−5</sup>),CD28-CD127-CD25++CD8brAC(OR=0.875,95%CI=0.814~0.942,<italic>P</italic>=3.619×10<sup>−4</sup>).THCA was associated with an increased risk of Secreting Treg % CD4 Treg (OR=1.143, 95% CI=1.064~1.229, <italic>P</italic>=2.779×10<sup>−4</sup>) and CD19 on IgD+ CD24+ (OR=1.118, 95% CI=1.041~1.120, <italic>P</italic>=0.002).</p></sec><sec><title>Conclusions</title><p>These findings suggest the causal associations between immune cells and THCA by genetic means. Our results may have the potential to provide guidance for future clinical research.</p></sec>