Journal Article

Heterogeneity of PD-L1 Expression and Relationship with Biology of NSCLC

LIBERATI, FABRIZIO, GIACINTI, SILVANA, STADDON, ANITA, BASSANELLI, MARIA, SIOLETIC, STEFANO, VITERBO, ANTONELLA, MARTINI, MAURIZIO, CERIBELLI, ANNA

2018

Overview

Immunotherapy with monoclonal antibodies against programmed cell death (PD-1), such as nivolumab and pembrolizumab, has significantly improved the survival of patients with metastatic non-small cell lung cancer (NSCLC). In order to determine the subset of patients that can benefit most from these therapies, biomarkers such as programmed death ligand-1 (PD-L1) have been proposed. However, the predictive and prognostic role of the use of PD-L1 is controversial. Anti-PD-L1 immunohistochemistry may not represent the actual status of the tumour because of individual variability and tumour heterogeneity. Additionally, there may be analytical variability due to the use of different assays and antibodies to detect PD-L1. Moreover PD-L1 expression is also regulated by oncogenic drivers in NSCLC, such as epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4 (EML4) fusion with anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS). Preclinical studies have shown the potential role of targeted therapy in immune escape mechanisms in NSCLC cells. This review summarizes current literature data on the heterogeneity of PD-L1 expression and the relationship with such factors and with clinicopathological features of NSCLC.

• Publisher: International Institute of Anticancer Research
• Subject: Adjuvants / Antineoplastic Agents - therapeutic use / Apoptosis / B7-H1 Antigen - immunology / B7-H1 Antigen - metabolism / Biomarkers / Cancer therapies / Carcinoma, Non-Small-Cell Lung - metabolism / Carcinoma, Non-Small-Cell Lung - pathology / Carcinoma, Non-Small-Cell Lung - therapy / Cell death / Cell growth / Chemotherapy / Combined Modality Therapy / Epidermal growth factor / Epidermal growth factor receptors / Genes, ras / Growth factors / Heterogeneity / Histology / Humans / Immunohistochemistry / Immunotherapy / Kinases / Ligands / Lung cancer / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Lung Neoplasms - therapy / Lymphoma / Medical prognosis / Metastases / Monoclonal antibodies / Mutation / Non-small cell lung carcinoma / Oncogene Proteins, Fusion - genetics / PD-1 protein / PD-L1 protein / Pembrolizumab / Prognosis / Protein Kinase Inhibitors - therapeutic use / Protein-tyrosine kinase / Proteins / Receptor, Epidermal Growth Factor - metabolism / Sarcoma / Small cell lung carcinoma / Tumors