Clinicopathological significance of peritumoral alveolar macrophages in patients with resected early-stage lung squamous cell carcinoma

Abstract

Introduction: This study aimed to clarify the correlation between the number of AMs and prognosis and to examine the gene expression of AMs in lung squamous cell carcinoma (SqCC). Methods: We reviewed 124 stage I lung SqCC cases in our hospital and 139 stage I lung SqCC cases in The Cancer Genome Atlas (TCGA) cohort in this study. We counted the number of AMs in the peritumoral lung field (P-AMs), and in the lung field distant from the tumor (D-AMs). Moreover, we performed a novel ex vivo bronchoalveolar lavage fluid (BALF) analysis to select AMs from surgically resected lung SqCC cases and examined the expression of IL10, CCL2, IL6, TGFβ, and TNFα (n=3). Results: Patients with high P-AMs had significantly shorter overall survival (OS) (p<0.01); however, patients with high D-AMs did not have significantly shorter OS. Moreover, in TCGA cohort, patients with high P-AMs had a significantly shorter OS (p<0.01). In multivariate analysis, a higher number of P-AMs was an independent poor prognostic factor (p=0.02). Ex vivoBALF analysis revealed that AMs collected from the tumor vicinity showed higher expression of IL10 and CCL2 than AMs from distant lung fields in all 3 cases (IL-10: 2.2, 3.0, and 10.0-fold; CCL-2: 3.0, 3.1, and 3.2-fold). Moreover, addition of recombinant CCL2 significantly increased the proliferation of RERF-LC-AI, a lung SqCC cell line. Conclusion: The current results indicated the prognostic impact of the number of peritumoral AMs and suggested the importance of peritumoral tumor microenvironment in lung SqCC progression.

Relationship of Tumor Necrosis Factor Alpha, Monocyte-Lymphocyte Ratio, and Neutrophil-Lymphocyte Ratio of Bronchial Washing Fluid with Histopathology, Stage, and Bronchoscopic Lesions of Non-Small Cell Carcinoma Lung Cancer

“…The difference in MLR between squamous and non-squamous NSCLC may be due to differences in cellular immune responses during the carcinogenesis process of the two types of lung cancer. A Japanese study showed an increased number of alveolar macrophages located close to the tumor cell collection (peritumoral) was an independent risk factor of poor prognosis for stage I squamous cell carcinoma lung cancer, illustrating the role of macrophages in the progression of squamous cell carcinoma lung cancer [20].…”