Beyond the PD-L1 horizon: In search for a good biomarker to predict success of immunotherapy in gastric and esophageal adenocarcinoma.

Gastric adenocarcinoma and esophageal adenocarcinoma are aggressive cancers with a poor prognosis. Therefore, new therapeutic strategies are needed, especially for patients refractory to conventional treatment. Cancer immunotherapy (CIT), is a promising new treatment option and is effective in a proportion of patients with gastroesophageal malignancies. Biomarkers for selecting patients likely to benefit from CIT in gastroesophageal malignancies remain unproven. Programmed cell death ligand-1 (PD-L1), which is a validated biomarker in non-small cell lung cancer (NSCLC), is often also used to select patients for CIT in the context of gastroesophageal cancer, although this marker has not been validated for this purpose. We question the use of PD-L1 as a biomarker in gastroesophageal cancers, as there are fundamental differences in PD-L1 expression between NSCLC and gastroesophageal cancers. This review discusses the value of PD-L1 in selecting patients for CIT in esophageal and gastric cancer. Potential alternatives, especially microsatellite instability and Epstein-Barr virus positivity, are discussed.