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According to the GLOBOCAN, gastric cancer is the fifth most common cause of cancer and the third most frequent cause of cancer-related death, in both sexes, all over the world. It often presents late in life, bearing a poor overall survival. Mass screening programs are not cost-effective in most countries and therefore primary prevention and personalized treatment are regarded as the best options to reduce gastric cancer mortality. Immune inhibitory checkpoints, such as Programmed cell Death-1 (PD-1):Programmed cell Death-Ligand 1 (PD-L1), allow the tumor to evade immune destruction - a potential new hallmark of cancer, through innate and adaptive immune resistance mechanisms. PD-1 monoclonal antibodies, nivolumab and pembrolizumab, are already approved therapies for advanced stage melanoma. This review addresses PD-L1 significance in infection persistence and gastric cancer development, providing rationale for PD-L1 targeted therapies.