Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage i pulmonary squamous cell carcinoma
Journal
European Journal of Cancer
Journal Volume
57
Pages
91-103
Date Issued
2016
Abstract
Background Programmed cell death-ligand 1 (PD-L1) is expressed in a subgroup of lung cancer that may benefit from immunotherapy. The interaction between PD-L1 expression and tumour infiltrating lymphocytes (TIL) remains poorly understood. This study investigated the expression of PD-L1 in surgically resected stage I pulmonary squamous cell carcinoma (SqCC) and correlated it with TILs in tumour microenvironments, common driver mutations, and clinical outcomes. Materials and methods One hundred and five patients with surgically resected stage I squamous cell carcinoma were examined. Paraffin-embedded tumour sections were stained with PD-L1 antibody. Tumours with moderate-to-strong membrane staining in ?5% of tumour cells were scored as positive for PD-L1 expression. The driver mutation epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) were examined by direct sequencing, while anaplastic lymphoma kinase (ALK), phosphoinositide 3-kinase catalytic alpha (PI3KCA), and fibroblast growth factor receptor 1 (FGFR1) were analysed by immunohistochemistry. The correlations of PD-L1 expression with each subtype of TIL, driver mutations, clinicopathologic parameters, and clinical outcomes were analysed. Results There was positive PD-L1 expression in 56.2% (59/105) of patients. PD-L1 expression was not associated with the common clinicopathologic features and mutations of EGFR, KRAS, BRAF, ALK, PI3KCA, and FGFR1. As regards TILs composition, tumour PD-L1 expression was significantly associated with increased tumour epithelial CD8+ T cells and stromal CD4+ T cells. Otherwise, PD-L1 (+) tumour cells were negatively correlated with PD-L1 (+) immune cells within tumour stroma. By multivariate analysis, tumour PD-L1 expression and increased CD4+ T cell infiltrations in the tumour stroma were independent predictors of better overall survival and had a trend of better disease-free survival. Conclusions PD-L1 expression is associated with a favourable immune microenvironment in stage I pulmonary SqCC and correlates with better clinical outcome. ? 2016 Elsevier Ltd. All rights reserved.
SDGs
Other Subjects
anaplastic lymphoma kinase; B Raf kinase; epidermal growth factor receptor; fibroblast growth factor receptor 1; K ras protein; phosphatidylinositol 3 kinase; phosphatidylinositol 3 kinase alpha; programmed death 1 ligand 1; unclassified drug; anaplastic lymphoma kinase; B Raf kinase; BRAF protein, human; CD274 protein, human; EGFR protein, human; epidermal growth factor receptor; forkhead transcription factor; FOXP3 protein, human; KRAS protein, human; phosphatidylinositol 3 kinase; PIK3CA protein, human; programmed death 1 ligand 1; protein p21; protein tyrosine kinase; adult; aged; Article; cancer prognosis; cancer staging; cancer survival; cancer tissue; CD4+ T lymphocyte; CD8+ T lymphocyte; controlled study; disease free survival; female; gene mutation; human; human tissue; immunohistochemistry; major clinical study; male; mutational analysis; outcome assessment; overall survival; priority journal; protein expression; squamous cell lung carcinoma; tumor microenvironment; genetics; immunology; Kaplan Meier method; lung tumor; metabolism; middle aged; mortality; mutation; prognosis; squamous cell carcinoma; tumor microenvironment; very elderly; Adult; Aged; Aged, 80 and over; Antigens, CD274; Carcinoma, Squamous Cell; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Forkhead Transcription Factors; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Phosphatidylinositol 3-Kinases; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Receptor Protein-Tyrosine Kinases; Receptor, Epidermal Growth Factor; Receptor, Fibroblast Growth Factor, Type 1; Tumor Microenvironment
Publisher
Elsevier Ltd
Type
journal article