Does Anti-Vascular Therapy Reprogram the Immunosuppressive Microenvironment in Gastric Cancer?

Abstract

Abnormal cell proliferation, a characteristic of malignant tumors, is accompanied by angiogenesis, through a complex molecular pathway involving various vascular growth factor groups. The abnormal blood vessels formed by the cancer establish a hypoxic and low pH environment in the vicinity of the tumor, causing a decrease in immunogenicity. Since the cancer cells produce immunosuppressive factors that further induce the related cells, an immunosuppressive environment optimal for the growth of the tumor is established. Although the gastrointestinal tract maintains homeostasis by specific immune surveillance mechanisms involving the lymph nodes and Peyer's patch, once a malignant tumor develops, a system that escapes the monitoring mechanism by taking advantage of the immune-checkpoint route is newly generated. Although normalization of the tumor microenvironment using molecular target drugs has attracted attention in recent years as the next generation cancer treatment, it is reported that this method also affects the host immune mechanism simultaneously. However, since many aspects of this intervention including the detailed mechanism of the immune mechanism for tumor microenvironment normalization, the prognosis, and the side-effects are still unclear, the clinical applications are not feasible yet. We believe that "normalization of the tumor environment and tackling its mechanism," can construct a host environment that maximizes the therapeutic effect of anti-cancer therapies including chemotherapy, immunotherapy, and radiation therapy, in addition to restoring the host immunity of the gastrointestinal tract. In other words, this could become the next generation cancer treatment. This review article focuses on tumor angiogenesis, tumor microenvironment, and the specific immune surveillance mechanism of the gastrointestinal tract, and finally proposes what is necessary for the "reprogramming of tumor microenvironment".