Insight into the significance of CD8+ tumor‐infiltrating lymphocytes in squamous cell lung cancer

Abstract

Abstract Background Although there are great expectations regarding the use of tumor‐infiltrating lymphocytes (TILs) to predict effects of immunotherapies and prognosis, knowledge about TILs remains insufficient for clinical application. Methods We objectively investigated the prognostic significance of tumor‐infiltrating CD8 + lymphocytes (CD8 + TILs) in squamous cell lung cancer (SQ‐LC). Among patients who underwent surgical resection of SQ‐LC in 2011–2017, 100 patients with pathological stage IA3‐III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma and parenchyma. The impact of CD8 + TILs on relapse‐free survival was analyzed using a Kaplan–Meier survival analysis and multivariate analyses using Fine‐Gray and Cox proportional hazards models. Results The multivariate analysis showed that large and small numbers, but not intermediate numbers, of CD8 + TILs in the tumor stroma may be related to a more favorable prognosis (small vs. intermediate: HR, 0.64; 95% CI: 0.29–1.41, p = 0.27; large vs. intermediate: HR, 0.48; 95% CI: 0.21–1.09, p = 0.08). In contrast, a large number of CD8 + TILs in the tumor parenchyma was associated with a poor prognosis (HR, 2.60; 95% CI: 0.91–7.42, p = 0.075). An exploratory analysis showed a potentially strong association between an extremely large number of CD8 + TILs in the tumor parenchyma and a poor prognosis, even with a large number of CD8 + TILs in the tumor stroma. Conclusion Our study provided partial but important information on the significance of CD8 + TILs in SQ‐LC. To use CD8 + TILs as biomarkers, a better understanding of CD8 + TILs as well as other important components in the tumor microenvironment and the inflammatory phenotypes they form may be needed.

Keywords

• biomarker
• immune checkpoint inhibitors
• lung cancer
• tumor microenvironment
• tumor‐infiltrating lymphocytes