Immature Granulocytes and Nivolumab Outcomes in Stage IV Non-Small Cell Lung Cancer: Insights by Tumor Subtype.

Abstract

Background: In non-small cell lung cancer (NSCLC) treatment, immunotherapy has become the standard therapy when platinum-based chemotherapy is ineffective, in the absence of a targetable mutation. However, a significant proportion of patients do not benefit from this treatment, underscoring the critical need for predictive biomarkers. This study aims to investigate the potential predictive role of immature granulocytes in response to nivolumab treatment, which can be used as a second-line therapy independent of programmed death ligand 1 (PDL-1) expression and other markers. Furthermore, the study seeks to determine whether there is a difference in the treatment response of immature granulocytes between the 2 main subtypes of NSCLC: lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD).

Methods: This retrospective study enrolled 50 patients with NSCLC who underwent treatment at the Kütahya Health Sciences University Evliya Çelebi Education and Research Hospital and Kütahya City Hospital between January 2021 and January 2025. The study examined the difference between patients' baseline immature granulocyte levels and their initial response to treatment, as assessed by positron emission tomography-computed tomography.

Results: The study found a statistically significant association between higher baseline immature granulocyte levels and poorer treatment response. Subgroup analysis by lung cancer subtype revealed that the difference was more prominent in the LUSCs group.

Conclusion: Immature granulocytes may predict response to nivolumab treatment in NSCLC patients, particularly in the LUSCs subgroup. Based on the findings of this study, immature granulocytes and other neutrophil-dependent inflammatory markers could serve as potential predictors of immunotherapy response and provide insights into the mechanisms of immunotherapy resistance, warranting further investigation. Our study may also encourage future research to look for separate markers for LUSCs and LUADs, given the continued critical need for predictive markers in this field.