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

Thorac Cancer. 2024 Feb;15(4):299-306. doi: 10.1111/1759-7714.15187. Epub 2023 Dec 20.

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.

MeSH terms

  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Squamous Cell* / pathology
  • Epithelial Cells / pathology
  • Humans
  • Lung Neoplasms* / pathology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Tumor Microenvironment