Tumor-associated neutrophils and macrophages in non-small cell lung cancer: no immediate impact on patient outcome

Abstract

Introduction: A tumor-promoting impact of neutrophils and macrophages has been demonstrated in some cancers. However, the prognostic significance of innate immune cells in patients with non-small cell lung cancer (NSCLC) is unclear.

Methods: A total of 335 consecutive patients resected for stage I-IIIA NSCLC were assessed for CD66b(+) neutrophils and CD163(+) macrophages in the tumor nests and adjacent stromal tissue by immunohistochemistry in whole tissue sections using stereology as well as automatic computerized quantification. Findings were correlated with clinical and histopathological parameters, baseline blood inflammatory markers (C-reactive protein (CRP) and white blood cell count (WBC)). Endpoints were recurrence-free survival (RFS) and overall survival (OS).

Results: Elevated CRP above median (101 nmol/l) and WBC above median (8.6 × 10(9)cells/l) were associated with poor RFS (p ≤ 0.002) and poor OS (p ≤ 0.01). Higher density of CD66b(+) in tumor nests and stroma was associated with elevated CRP and WBC, squamous cell histology, tumor size, and necrosis (p ≤ 0.01). Higher density of CD163(+) macrophages in tumor nests and stroma was associated with elevated CRP and lymph node metastases (p ≤ 0.049). The densities of tumor nest CD66b(+) neutrophils and CD163(+) macrophages were not significantly correlated with RFS or OS, irrespective of assessment method.

Conclusions: The densities of tumor-associated CD66b(+) neutrophils and CD163(+) macrophages in NSCLC were correlated with adverse prognostic factors and systemic blood inflammation markers, but not directly correlated with RFS or OS. Further research of chronic inflammation in NSCLC is warranted.