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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.

Original publication

DOI

10.1007/s00428-018-2483-1

Type

Journal article

Journal

Virchows Arch

Publication Date

02/2019

Volume

474

Pages

159 - 168

Keywords

IDO-1, Immunotherapy, Non-small cell lung cancer, PD-L1, Tumor-infiltrating lymphocytes, Adenocarcinoma, Aged, Aged, 80 and over, B7-H1 Antigen, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung, Disease-Free Survival, Female, Humans, Immunohistochemistry, Indoleamine-Pyrrole 2,3,-Dioxygenase, Kaplan-Meier Estimate, Lung Neoplasms, Lymphocytes, Tumor-Infiltrating, Male, Middle Aged, Prognosis, Survival Rate