Abstract
Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype. The new molecular classification of gastric cancer also takes these factors into consideration. Available reports regarding PD-1, PD-L1, PD-L2 expression and MSI status in gastric and esophageal cancer are reviewed to summarize the clinical prognostic and predictive role together with potential clinical implications. The most important recently published clinical trials evaluating checkpoint inhibitor efficacy in these tumors are also summarized.
Highlights
Esophageal and gastric cancers are among the top ten most frequent and deadly tumors worldwide [1]
The aim of the present review is to summarize the recent developments of immunotherapy in gastric and esophageal cancers with reference to key developments in other epithelial cancers
The mechanism for PD-L1 expression is probable related to latent membrane protein 1 (LMP1) and interferon-gamma stimulated by Epstein-Barr virus (EBV) which upregulate the expression of PD-L1 [47]
Summary
Esophageal and gastric cancers are among the top ten most frequent and deadly tumors worldwide [1] The etiology of both tumors is poorly understood, but bacterial, viral, and environmental factors are thought to play a substantial role. One of the fundamental evasion mechanisms of cancer cells, defined by Hanahan and Weinberg as “hallmarks of cancer”, is the alteration of the host immune system which allows tumor growth in a relatively hostile environment. Tumor cells can use this mechanism to catalyze the auto-destruction of the immune response. These mechanisms are at the center of interest of the research aiming to sustain the activity of the immune system to allow the tumor cells to be destroyed, and acting on the immune checkpoints seems to be a promising option. The aim of the present review is to summarize the recent developments of immunotherapy in gastric and esophageal cancers with reference to key developments in other epithelial cancers
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