AUTHOR=Li Lan , Sun Yeqi , Luo Jia , Liu Mengjiao TITLE=Circulating immune cells and risk of osteosarcoma: a Mendelian randomization analysis JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1381212 DOI=10.3389/fimmu.2024.1381212 ISSN=1664-3224 ABSTRACT=Objectives

Osteosarcoma (OS) is the primary bone tumor originating from transformed mesenchymal cells. It is unclear whether associations between specific circulating immune cells and OS are causal or due to bias. To clarify whether predicted genetically altered circulating immune cells are associated with OS development, we performed a two-sample Mendelian randomization (MR) analysis.

Methods

The genetic variants strongly associated with immune cell traits as instrumental variables (IVs) were used to perform MR analyses. The effect of specific immune cells on OS risk was measured using the summary statistics from the genome-wide association studies (GWAS).

Results

Our findings indicate that CD80 on CD62L+ myeloid dendritic cell and CD28−CD4−CD8− T-cell absolute count are positively associated with OS (CD80 on CD62L+ myeloid dendritic cell, OR: 3.41 [95% CI: 1.40 to 8.31], p = 0.007; CD28−CD4−CD8− T-cell absolute count, OR: 4.49 [95% CI: 1.29 to 15.62], p = 0.018). It is also found that CD20 has a negative effect on CD24+CD27+ B cell on OS (OR: 0.32 [95% CI: 0.14 to 0.72], p = 0.006) and a similar impact on IgD+ CD38− B cell on OS (OR: 0.19 [95% CI: 0.05 to 0.68], p = 0.011).

Conclusions

These findings illustrate that the genetic predisposition to specific immune cells can exert a causal effect on OS risk, which confirms the crucial role played by immunity in OS development. Particularly, the causal association between immune cells and OS underscores the evidence for exploring the new treatment strategy for OS in the future.