Immunotherapy in gastric cancer

Abstract

Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.

Report from the 17th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Edmonton, Alberta; 11–12 September 2015

“…The PD-1 molecule negatively regulates and downregulates T cell responses, and eventually apoptosis is initiated after a PD-1 ligand binds with PD-1. The PD-1 ligands PD-L1 and PD-L2 are frequently expressed on tumour cells and can thus thwart the immune response 107 . One approach to overcome that immune response inhibition has been to target immune checkpoints w ith blocking monoclonal antibodies.…”

MicroRNA-34 dysregulation in gastric cancer and gastric cancer stem cell

“…For advanced forms of the disease, the treatment consists of a combination of surgery, chemotherapy and radiation. Overall, the results of current therapy for advanced disease are poor, 2 and the 5-year survival rate is still less than 40%. 4,5 Thus, new and effective strategies for cancer therapy should be established through further research, by providing precise knowledge of key molecular mechanisms by which a cancer cell is deregulated.…”

Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis

“…Gastric cancer (GC) is one of the most common cancers, and is the fifth most common type worldwide [1]. It is the second most common cause of cancer-related deaths after lung cancer [2,3].…”