Immune Microenvironment Differences Between Squamous and Non-squamous Non-small-cell Lung Cancer and Their Influence on the Prognosis.
Antibodies, Monoclonal
/ therapeutic use
CD8-Positive T-Lymphocytes
/ immunology
Carcinoma, Non-Small-Cell Lung
/ diagnosis
Carcinoma, Squamous Cell
/ diagnosis
Cellular Microenvironment
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Immunotherapy
/ methods
Lung Neoplasms
/ diagnosis
Lymphocytes, Tumor-Infiltrating
/ immunology
Male
Middle Aged
Neoplasm Staging
Prognosis
Programmed Cell Death 1 Receptor
/ immunology
Immune microenvironment
NSCLC
PD-L1
Prognoses
TILs
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
28
12
2017
revised:
12
09
2018
accepted:
18
09
2018
pubmed:
21
10
2018
medline:
27
6
2019
entrez:
21
10
2018
Statut:
ppublish
Résumé
Checkpoint blockades have entered routine clinical use for non-small-cell lung cancer (NSCLC). However, there were some differences in efficacy and response predictors for anti-programmed cell death protein 1 (PD-1) antibodies between squamous (SQ) and nonsquamous (non-SQ) NSCLC. The study aims to elucidate the possible difference in immune microenvironment between SQ-NSCLC and non-SQ-NSCLC and their influence on the prognosis. A total of 197 patients with stages I to III NSCLC were included. cluster of differentiation 8 (CD8), cluster of differentiation 4 (CD4), transcription factor forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) expression were examined in cancer nest and stroma on 85 SQ-NSCLC and 112 non-SQ-NSCLC samples using immunohistochemistry. More CD8+ tumor infiltrating lymphocytes (TILs) were detected in the cancer nests (cCD8) from patients with SQ-NSCLC than those with non-SQ-NSCLC (56% vs. 34%; P = .002). There were no significant differences between the SQ and non-SQ groups in terms of other TIL markers or PD-L1 expression. Multivariate analysis showed that the degree of cCD8+ TIL infiltration was an independent positive predictor for overall survival (OS) in the SQ-NSCLC group (P = .003) and in the non-SQ-NSCLC group (P = .024). In the univariate analysis, CD8+ TILs in the stroma, CD4+ TILs in the cancer nest and stroma, and FOXP3+ TILs in the cancer stroma associated with different prognoses for patients with either non-SQ-NSCLC or SQ-NSCLC. Using a 10% cutoff, PD-L1 expression was a poor prognostic factor in total NSCLC (P = .011), stage I (P = .037), SQ-NSCLC (P = .097), and non-SQ-NSCLC (P = .051). The different cCD8+ TIL profile and different prognostic value with certain TILs indicates that SQ-NSCLC and non-SQ-NSCLC are likely different cancer types with respect to their immune microenvironments.
Identifiants
pubmed: 30341017
pii: S1525-7304(18)30257-2
doi: 10.1016/j.cllc.2018.09.012
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
48-58Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.