Programmed death ligand 1 immunohistochemistry in non-small cell lung carcinoma

Lung cancer is the most common cause of cancer-related death, responsible for nearly 1.8 million new cases diagnosed and 1.6 million deaths worldwide per year (1). Approximately 85% are non-small cell lung carcinoma (NSCLC), with more than 50% of adenocarcinoma and 30% of squamous cell carcinoma. Most patients present with advanced stage disease at the time of diagnosis (70%) and in the vast majority, only small samples, i.e., biopsies or cytology specimen, are available for diagnosis and biomarker testing. Less than half of lung adenocarcinoma harbor targeted driver EGFR, BRAF and HER2 mutations or ALK or ROS1 rearrangements, but in other NSCLC with no targeted molecular abnormalities the only therapeutic option was until recently conventional platinum-based doublet therapy, with pemetrexed maintenance for non-squamous NSCLC (2,3). This option offered a median overall survival of 1- and 5-year survival of 15%, all stages included. Since 2014, immunotherapies targeting programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) were evaluated in clinical trials, in monotherapy or in combination with chemotherapy or anti-CTLA4 agents, showing for a subset of patients a clear benefit with increased progression-free survival and overall survival. These immunotherapies are now available in routine practice and biomarkers predicting clinical response are complementary or mandatory for some drugs to better select patients who will benefit from immunotherapy