Common strategies for effective immunotherapy of gastroesophageal cancers using immune checkpoint inhibitors

Gastroesophageal cancers (GECs) are very prevalent around the world and rank as the second cause of all cancer-related deaths in men and women and demonstrate a very poor prognosis. Currently, the treatment options for these malignancies are very limited and the response rates are also very low. Recently, immune checkpoint inhibitors (ICIs) have been proposed for immunotherapy of GECs; although preliminary results obtained from the clinical trials of ICIs in GECs were promising, they have shown to be effective only in a few subsets of patients who had a previous immune response to the tumor. In order to maximize the efficacy of ICIs in GECs, as well as identify the patients who will likely benefit from ICIs, several predictive biomarkers, such as Programmed death-ligand 1 (PD-L1) have been developed and evaluated. Since the single ICI therapies resulted in poor treatment response, several clinical studies began to explore various combinations of one or two ICIs with other anti-cancer treatment approaches, including chemotherapy, radiotherapy, and anti-angiogenesis therapy. These combinations demonstrated a more effective response among the ICIs-responsive patients and even in some instances sensitized the non-responsive individuals. This review is aimed to summarize the efforts made so far for improving the effectiveness of ICIs in the treatment of patients with GECs. Furthermore, multiple aspects of translational medicine such as available biomarkers and interactions between tumor and the immune system, as well as clinical aspects regarding the combination therapies and results of clinical trials will be discussed.