Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications

Virchows Arch. 2019 Feb;474(2):159-168. doi: 10.1007/s00428-018-2483-1. Epub 2018 Nov 17.

Abstract

Several cancers, especially non-small cell lung cancer (NSCLC), are able to escape the immunosurveillance of tumor-infiltrating lymphocytes (TILs); among the molecules involved, the indoleamine 2,3-dioxygenase 1 (IDO-1) and the programmed cell death ligand-1 (PD-L1) play a crucial role. These aspects are of great interest in the current immunotherapeutic era, therefore the current study analyses the TILs, IDO-1, and PD-L1 interactions and their correlations with clinicopathological parameters and prognosis in NSCLC. One hundred ninety-three NSCLC surgical specimens, formalin-fixed, and paraffin-embedded were assessed for TILs density, TILs localization, IDO-1 (clone 4.16H1), and PD-L1 (clone E1L3N) immunohistochemical expressions. This data was correlated with clinicopathological parameters, disease free, and overall survivals. IDO-1 and PD-L1 high expressions were related to the solid pattern of adenocarcinomas (respectively p = 0.036 and p = 0.026); high PD-L1 expression was correlated with squamous histotype (p = 0.048). IDO-1 overexpression correlated with former smokers (p = 0.041), higher adenocarcinoma stages (p = 0.039), and with both higher TILs density and PD-L1 expression (respectively p = 0.025 and p = 0.0003). A better prognosis was associated with TILs intratumoral or mixed localizations (p = 0.029). TILs localization affects NSCLC prognosis; the higher expression of IDO-1 and PD-L1 in poorly differentiated and more aggressive lung adenocarcinomas, as well as the correlation between high PD-L1 expression and squamous cell histotype, confirm the more efficient immunoescaping of these NSCLC subgroups.

Keywords: IDO-1; Immunotherapy; Non-small cell lung cancer; PD-L1; Tumor-infiltrating lymphocytes.

MeSH terms

  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / classification
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Survival Rate

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase