The association between white blood cell count and relative risk of non-small cell lung cancer

High abundance of eosinophils has been proved to associated with favorable disease progression in non-small cell lung cancer (NSCLC) in the previous observational studies, but the causal relationship remains unclear. It is also unclear whether white blood cell (WBC) counts are essential for the risk of NSCLC.

Using multiple methods of Mendelian randomization (MR), we assessed the causality of WBC count, particularly basophil, eosinophil, monocyte, lymphocyte, and neutrophil counts on the risk of NSCLC, which includes squamous carcinoma and adenocarcinoma. Single cell RNA-sequencing and RNA-sequencing analysis illustrate the underline mechanism of the causality and its biological effects.

Univariable MR analysis indicated the protective effect of elevated eosinophil counts on NSCLC and adenocarcinoma subtype. The protective effect of eosinophils persisted even after adjusting. The protective functions mainly effected by immune activating, and it contribute to better survival and favorable response to immune therapy. Univariate MR analysis also states the risk role of neutrophil. Sequencing based analysis proved the immune inhibit functions of neutrophil, which lead to worse survival and immune treatment response.

Our study indicated a correlation between circulating eosinophil counts, neutrophil counts, and the development of NSCLC. And sequencing analysis confirm this relationship and illustrated the underline mechanism.