Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage I pulmonary squamous cell carcinoma.

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.

• Authors: Ching-Yao Yang, Mong-Wei Lin, Yih-Leong Chang, Chen-Tu Wu, Pan-Chyr Yang
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 57 Pg. 91-103 (Apr 2016) ISSN: 1879-0852 [Electronic] England
• PMID: 26901614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• FOXP3 protein, human
• Forkhead Transcription Factors
• KRAS protein, human
• Phosphatidylinositol 3-Kinases
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human
• ALK protein, human
• Alk protein, rat
• Anaplastic Lymphoma Kinase
• EGFR protein, human
• ErbB Receptors
• Receptor Protein-Tyrosine Kinases
• Receptor, Fibroblast Growth Factor, Type 1
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Proto-Oncogene Proteins p21(ras)

Topics

• Adult
• Aged
• Aged, 80 and over
• Anaplastic Lymphoma Kinase
• B7-H1 Antigen (metabolism)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinoma, Squamous Cell (genetics, immunology, mortality)
• Class I Phosphatidylinositol 3-Kinases
• ErbB Receptors (genetics, metabolism)
• Female
• Forkhead Transcription Factors (metabolism)
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (genetics, immunology, mortality)
• Male
• Middle Aged
• Mutation (genetics)
• Phosphatidylinositol 3-Kinases (metabolism)
• Prognosis
• Proto-Oncogene Proteins B-raf (genetics, metabolism)
• Proto-Oncogene Proteins p21(ras) (genetics, metabolism)
• Receptor Protein-Tyrosine Kinases (metabolism)
• Receptor, Fibroblast Growth Factor, Type 1 (metabolism)
• Tumor Microenvironment (immunology)