Tumour immune microenvironment in resected thymic carcinomas as a predictor of clinical outcome

The spatial distribution of tumour-infiltrating lymphocytes (TILs) is a novel descriptor characterising the tumour immune microenvironment (TIME). The aim of our study was to assess whether a specific TIME of surgically resected thymic carcinoma (TC) can predict tumour invasiveness, recurrence or su...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 2022-10, Vol.127 (6), p.1162-1171
Main Authors: Bocchialini, Giovanni, Schiefer, Ana-Iris, Müllauer, Leonhard, Thanner, Jürgen, Bauer, Jonas, Thaler, Felizia, Laggner, Maria, Veraar, Cecilia, Klepetko, Walter, Hötzenecker, Konrad, Matilla, José Ramon, Ankersmit, Hendrik Jan, Moser, Bernhard
Format: Article
Language:English
Subjects:
Apoptosis
B7-H1 Antigen
Cancer therapies
Carcinoma
CD3 antigen
CD4 antigen
CD56 antigen
CD8 antigen
CD8-Positive T-Lymphocytes
Forkhead Transcription Factors
Foxp3 protein
Humans
Immune checkpoint inhibitors
Immune system
Invasiveness
Lymphocytes
Lymphocytes, Tumor-Infiltrating
Microenvironments
Microscopy
Open source software
Pathology
Patients
PD-1 protein
PD-L1 protein
Phenotypes
Prognosis
Radiation
Reproducibility
Spatial distribution
Thoracic surgery
Thymoma - pathology
Thymus
Thymus Neoplasms - pathology
Thymus Neoplasms - surgery
Tumor Microenvironment
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The spatial distribution of tumour-infiltrating lymphocytes (TILs) is a novel descriptor characterising the tumour immune microenvironment (TIME). The aim of our study was to assess whether a specific TIME of surgically resected thymic carcinoma (TC) can predict tumour invasiveness, recurrence or survival. Digital microscopy was performed on 39 TCs immunohistochemically stained to investigate the activation of the immune checkpoint pathway (PD-L1/PD-1), along with density and spatial distribution of TILs phenotypes (CD3+, CD4+, CD8+, FOXP3+, CD56+). The impact of PD-L1 and TIL density considering the intratumoural (iTILs) and stromal (sTILs) distribution on pathological characteristics and clinical outcomes were analysed. In early TC stages, we observed a higher total density of CD3+ (p = 0.05) and CD8+ (p = 0.02) TILs. PD-L1 was expressed in 71.8% of TCs. In advanced TC stages, we observed a lower density of CD3+ (p = 0.04) and CD8+ (p = 0.01) iTILs compared to early stages. Serum concentrations of PD-L1 were significantly higher in TCs compared to healthy controls: 134.43 ± 18.51 vs. 82.01 ± 6.34 pg/ml (p = 0.001), respectively. High densities of stromal CD4+ TILs (54 vs. 32%, p = 0.043) and CD8+ TILs (65 vs. 17%, p = 0.048) were associated with improved freedom from recurrence (FFR) and cause-specific survival (CSS). High density of FoxP3+ TILs were associated with improved FFR (p = 0.03) and CSS (p = 0.003). Mapping TIL subpopulations complement the armamentarium for prognostication of TC outcomes. The improved outcome in patients with high density of TILs supports the use of immune checkpoint inhibitors in TC patients.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-022-01875-7