Insight Into the Significance of CD8+ Tumor-Infiltrating Lymphocytes in Lung Adenocarcinoma.

Abstract

Background: Despite great expectations regarding the use of tumor-infiltrating lymphocytes (TILs) in predicting the effects of immunotherapies and prognosis, knowledge about TILs remains inadequate for clinical application. We re-evaluated the clinicopathological significance of CD8+ tumor-infiltrating lymphocytes (CD8 + TILs) in lung adenocarcinoma from a novel perspective and through a more objective approach using cell counting software.

Methods: Among patients with surgical resection of lung adenocarcinoma in 2011-2017, 156 patients with pathological stage IB-III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma. The impact of CD8 + TILs on relapse-free survival was analyzed by Kaplan-Meier survival and multivariate Cox proportional hazards analyses.

Results: Our analysis showed that patients with large numbers of CD8 + TILs in the stroma are not a homogeneous population and include subpopulations with a poor prognosis. Furthermore, our study showed important findings about the overall inflammatory status in the tumor microenvironment based on the association between the number of CD8 + TILs and the frequency of vascular invasion. Additionally, CD8 + TILs were shown to potentially be more effective than PD-L1.

Conclusions: Our study demonstrated that in lung adenocarcinoma, even among populations with abundant CD8 + TILs in the tumor stroma, there may be a poor prognostic subgroup. Furthermore, we revealed a partial yet important relationship between CD8 + TILs and the tumor microenvironment. A more detailed investigation into the significance of CD8 + TILs may lead to a deeper understanding of the inflammatory status of the tumor microenvironment and ultimately contribute to the identification of appropriate biomarkers for prognostic prediction and assessing the efficacy of immune checkpoint inhibitors.