Eosinophils as Predictive Biomarkers in Anti-Programmed Cell Death-1 Monotherapy for Non-Small Cell Lung Cancer

Takahiro Uchida^1*Kazuyuki Nakagome^1*Kosuke Hashimoto²Hidetoshi Iemura¹Yuki Shiko¹Atsuto Mouri²Ou Yamaguchi²Yoshitaka Uchida¹Yoshiaki Nagai¹Tomoyuki Soma¹Kyoichi Kaira²Makoto Nagata¹Hiroshi Kagamu^2*

• ¹Saitama Medical University, Saitama, Japan
• ²Saitama Medical University International Medical Center, Saitama, Japan

Background: The relationship between eosinophilia and cancer development has recently been investigated. However, the role of eosinophils in tumor immunity, particularly in the context of immune checkpoint inhibitor (ICI) therapy, remains poorly understood. Methods: We investigated the relationship between peripheral blood eosinophil and T-lymphocyte subsets and the clinical characteristics of patients undergoing anti-programmed cell death-1 (PD-1) monotherapy for non-small cell lung cancer (NSCLC). The study included 204 patients treated with nivolumab monotherapy, and clinical data and treatment responses were recorded. PBMCs were collected from 44 out of 204 patients before treatment to analyze T-lymphocyte subsets, focusing on their correlation with blood eosinophils. Results: The percentage of blood eosinophils before nivolumab treatment was positively correlated with the percentage of effector memory subsets in both CD4+ (r = 0.43, p = 0.0045) and CD8+ T cells (r = 0.35, p = 0.020). It was negatively correlated with the percentage of naïve subsets of CD4+ T cells and positively correlated with the percentage of inducible T cell co-stimulator cells among CD8+ T cells. Patients with higher eosinophil levels (≥1.7%) before nivolumab treatment exhibited significantly longer progression-free survival (log-rank p = 0.014) and overall survival (log-rank p = 0.001) than those with lower eosinophil levels. An early increase in the eosinophil count after treatment was also associated with a better response to nivolumab. Conclusion: Higher blood eosinophil levels may indicate activated T-cell immunity and may be a promising biomarker for the efficacy of anti-PD-1 monotherapy in patients with NSCLC.