Oncogenes Orchestrate Immunosuppressive Stroma in Gastric Adenocarcinoma

Gastric adenocarcinoma (GAC) is among the three most common cancers in the world. The majority of GAC patients are diagnosed in an advanced stage and have a median survival of ~9 months. There are limited effective therapeutic strategies available in the clinic and currently U.S. Food and Drug Administration (FDA) approved immune therapy is programmed death-1 (PD-1) antibodies (e.g. pembrolizumab) but only a few patients seem to benefit. Transformation to cancer occurs when multiple genes and cellular pathways are dysregulated in multi-cellular organisms. Mounting evidence supports that oncogenes orchestrate tumor immune suppressive stroma to foster tumor favoring microenvironmental niche. Thus, deeper understanding of the immunosuppressive mechanisms in tumor stroma especially orchestrated by notable oncogenes can allow exploration of novel avenues that may have an impact on patient outcome. In this review, we summarize current progress of notable oncogenes and pathways including Ras/Myc, EGFR/HER2, PI3K/mTOR, Wnt/β-catenin, and Hippo/YAP pathways focusing on the interplay between these oncogenic pathways and immunosuppressive stroma. Future potential novel targets and immune checkpoint blockage are discussed.