Expressions of CD8+TILs, PD-L1 and Foxp3+TILs in stage I NSCLC guiding adjuvant chemotherapy decisions

Oncotarget. 2016 Sep 27;7(39):64318-64329. doi: 10.18632/oncotarget.11793.

Abstract

Purpose: Currently, adjuvant chemotherapy is recommended for patients with high risk stage I non-small cell lung cancer (NSCLC). However, identifying high risk patients remains a challenge. This study aims to identify the patient cohorts more likely to benefit from adjuvant chemotherapy based on the tumor micro-immune environment.

Results: CD8+TILs significantly associated with disease-free survival (DFS) and overall survial (OS) (p=0.002; 0.040). Patients with high risk factors may also predict shorter DFS (P=0.056). When compared together, patients with high-CD8+TILs showed better DFS than patients with low-CD8+TILs, no matter their risk factors status. There's no correlation between PD-L1 expressions and survival. PD-L1 was highly expressed in men, squamous and well differentiated carcinoma. In addition, Foxp3+TILs alone didn't show any prognostic effects, but low-Foxp3/high-CD8+TILs were associated with prolonged DFS (p=0.031).

Methods: A total of 126 patients with surgically resected stage I NSCLC were included to perform immunohistochemistry of CD8+ tumor infiltrating lymphocytes (TILs), programmed death ligand-1(PD-L1) and forkhead box P3 (Foxp3)+TILs.

Conclusion: CD8+TILs are effective prognostic predictors. Patients with surgically resected stage I NSCLC showing low CD8+TILs could be considered for adjuvant chemotherapy, even if they have no high risk features.

Keywords: Foxp3; PD-L1; TILs; adjuvant chemotherapy; non-small cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / analysis*
  • Biomarkers, Tumor / analysis*
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Chemotherapy, Adjuvant
  • Clinical Decision-Making*
  • Disease-Free Survival
  • Female
  • Forkhead Transcription Factors / analysis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Patient Selection
  • Pneumonectomy
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors