Prognostic impact of tumor-infiltrating lymphocytes and neutrophils in resected non-small cell lung carcinoma

Abstract

The prognostic impact of tumor-infiltrating lymphocytes (TILs) has been determined in non-small cell lung carcinoma; however, there is no standardized method for counting TILs. In this report, we applied the method proposed by the International Immuno-Oncology Biomarkers Working Group for the assessment of TILs to count the number of tumor-infiltrating neutrophils (TINs). We then analyzed the association between TIL counts, TIN counts, and clinicopathological factors in lung cancer. We retrospectively analyzed a series of 1191 Japanese patients with resected lung adenocarcinoma and squamous cell carcinoma, which were restaged according to the eighth edition of the TNM staging system. Tumors were classified according to the 2015 WHO classification of lung carcinoma. Recurrence-free probability (RFP) and overall survival (OS) were analyzed using the log-rank test and Cox proportional hazard model. Using multivariate analysis for patient outcome in patients with adenocarcinoma, high TIN counts were an independent prognostic factor for worse RFP (hazard ratio [HR]: 1.94, p<0.001) and worse OS (hazard ratio [HR]: 1.75, p=0.006). On the other hand, TIL counts were not related to patient outcome. We have demonstrated that high TINs are unfavorable prognostic markers for resected lung adenocarcinoma. In resected lung squamous cell carcinoma, TIL and TIN counts were not related to patient prognosis. It has been suggested that the immune response to cancer cells may differ depending on the histological type. An understanding of how neutrophils are programmed to perform protumor activities is necessary for the future design of targeted immunotherapies.