Appraising the effectiveness of immune cells on thyroid cancer: a Mendelian randomization study

The intricate interplay between the immune system and tumor plays a pivotal role in thyroid cancer (TC) pathogenesis, potentially influencing both the causation and therapeutic outcomes. Despite extensive research, existing literature offers ambiguous insights regarding the association between immune cell traits and thyroid cancer progression.

To elucidate the potential causal relationships, we conducted an integrated two-sample Mendelian randomization (MR) analysis. This study utilized publicly genetic datasets to explore the causalities between 731 immune cell traits (categorized into four trait types across seven panels) and thyroid cancer. We ensured the robustness of our findings through comprehensive sensitivity analyses, meticulously assessing potential sources of bias such as pleiotropy.

After False Discovery Rate (FDR) correction, six immune cell traits were identified to be significantly associated with thyroid cancer risk (Inverse Variance Weighted, IVW): Absolute count of gamma delta T cells/ T-cell receptor gamma delta absolute count (TCRgd AC) 0.8464 (OR95% CI = 0.7477-0.9580, P = 0.0083, PFDR = 0.0103); CD8 on bright CD8 cells (CD8 on CD8br) 0.8867 (OR95% CI = 0.8159-0.9637, P = 0.0047, P_FDR = 0.0093); CD127 on CD45RA negative CD4 T cells not regulatory T cells (CD127 on CD45RA- CD4 not Treg) 0.8969 (OR95% CI = 0.8192-0.9820, P = 0.0186, P_FDR = 0.0186); CD80 on CD62L positive plasmacytoid dendritic cells (CD80 on CD62L+ plasmacytoid DC) 1.1091 (OR95% CI = 1.0267-1.1982, P = 0.0086, P_FDR = 0.0103); CD80 on plasmacytoid DC 1.1283 (OR95% CI = 1.0462-1.2168, P = 0.0017, P_FDR = 0.0093); Side scatter-area on bright CD8 cells (SSC − A on CD8br) 1.1622 (OR95% CI = 1.0507-1.2854, P = 0.0035, P_FDR = 0.0093).

Our study demonstrated the causalities between immune cell traits and thyroid cancers by Mendelian randomization study, thus guiding future mechanism studies.