Page 61 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Introduction:
Gastric cancer(GC) is a major public health problem and is the second most prominent cause of cancer-related death globally[1]. The incidence of GC, however, dramatically varies across different geographical areas, it being the highest in Japan, China, other Far Eastern countries, Russia, Middle Eastern area, and in the Pacific coast of the South American continent, whereas it is the lowest in Central Africa. Europe and North American regions share an intermediate-to-high incidence. Although only 25–30% of GC patients survive five years from the initial diagnosis, heterogeneity in survival rates is substantially and may relate to biological and genomic differences between Asian and Western populations[2]. The depressingly high mortality calls for better clinical management.
Currently, chemotherapy remains the mainstay in the treatment of advanced disease and involves a plethora of cytotoxic agents comprising platinum agents, fluoropyrimidines, anthracyclines, irinotecan and taxanes. At present combinatory chemotherapy regimens is the preferred first-line option as they result in better survival and response rates when matched to therapy involving single agents[3]. Nevertheless, it is fair to say outcomes are disappointing and alternatives are vigorously pursued. Strikingly, however, immunotherapy has been getting relatively little exposure in this respect.
Generally speaking, immunotherapy and especially immune checkpoint-directed therapy are now revolutionizing the management of oncological disease (indeed in 2013 the American Academy of science announced immunotherapy as the breakthrough of the year[4-6]). Cancers are antigenic and provoke immunity, but manage to escape their resulting destruction via a variety of mechanisms but also through activation of so-called checkpoints: inhibitory elements to limit self- damaging autoimmunity. The most prominent of this immune checkpoint inhibitory antibodies are those against cytotoxic T-lymphocyte antigen 4 (CTLA-4), receptor of programmed cell death 1 (PD-1) and its cognate ligand programmed death-ligand 1 (PD-L1). Figure 1 illustrates their mode of action and their efficacy includes a wide range of solid cancers in particular melanoma[7-9], cancer of the lung[10-12] and basal cell carcinoma[13]. Thus it is tempting to assume a possible efficacy for such checkpoint inhibitors for gastric cancer as well. Here we review the available public data and conclude that especially PD-1-directed therapy (Pembrolizumab,
Immunotherapy Checkpoint Inhibition
Immuno checkpoint inhibition
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