SY17-5 Potential biomarkers for immunotherapy of gastric cancer

Immune check point inhibitors (ICIs) such as PD-1/PD-L1 antibodies have been approved in patients with various cancers including gastric cancers. However, their responses are still limited. Thus, the identification of biomarkers to select appropriate patients and combination immunotherapies is needed. To solve these issues, it is essential to understand immunobiology of cancer, including mechanisms of action and resistance in the current immunotherapies. Immune status particularly in tumor microenvironments is different among patients, and is positively and negatively defined by cancer cell genetic characteristics, patients' genetic immune-reactivity, and environmental/lifestyle factors, and it influences responses to ICIs. Clinical samples including peripheral blood and tumors at baseline and post-treatment may be utilized for evaluation of biomarkers. Immune status and biomarkers may depend on cancer types and subtypes. In patients with gastric cancer treated with anti-PD-1Abs, potential biomarkers are being evaluated as follows: DNA mutation burden generating neo-antigens, MSI status, EBV positivity, various gene alterations (e.g. oncogene activation, SCNA, gene repair defect) and altered metabolisms have been proposed as tumor associated biomarkers, and PD-L1 expression in cancer cells or tumor infiltrating cells such as tumor associated macrophages, IFN/T effector signature, and T effector/T memory/T exhaustion/T regulatory dynamics as immune biomarkers, and gut microbiota and smoking as environmental/ life style related biomarkers. PD-1/PD-L1 Ab based combination immunotherapies with various immune modulators including chemotherapy and anti-VEGF therapy are currently being evaluated in clinical trials. Biomarkers may be different in the combination immunotherapy from those in the therapy with PD-1/PD-L1 alone. We will discuss the recent status of biomarkers in cancer immunotherapy, especially for patients with gastric cancers.