How Macrophages Regulate Stomach Cancer

Lay Abstract Stomach cancer is a lethal disease with grim prognosis. In 2020, it accounted for over a million cases worldwide ranking as the 4th most common cancer. It is the second leading cause of cancer-related deaths worldwide. In patients with metastatic stomach cancer, where the cancer has spread to other parts of the body, 5-year survival is only 5%. Peritoneal carcinomatosis is a condition where the cancer cells migrate from the stomach to the surface of the peritoneal cavity. The peritoneal cavity is the protective sac that houses all the abdominal organs. In stomach cancer, it is the most common site of metastasis, affecting about 50-60% of patients over their disease course. There is currently no cure for this condition. 100% of the patients affected will succumb to their disease and most of the fatalities will occur within 6-9 months of diagnosis. Unfortunately, our knowledge of how to treat this problem remains a mystery. In the last few decades, immunotherapy brought new hope for cancer patients. It is especially potent because it charges the body’s own immune system to fight cancer. It has been incredibly successful in treating skin and kidney cancer. Unfortunately, its benefit has been marginal in patients with peritoneal carcinomatosis. This is surprising because there are many immune cells that traffic in the peritoneal cavity. The purpose of this project is to discover new ways to charge the immune cells in the peritoneal cavity so that immunotherapy can become efficacious in this disease. Macrophages are a type of immune cell abundant in the peritoneal cavity. Their major function is to alert other cells that foreign substances such as tumor cells, bacteria or viruses are in the body. They can also help with eradication of tumor cells. When they malfunction, tumor cells have the freedom to grow incognito. We hypothesize that targeting macrophages to become more effective at identifying and eradicating tumor cells could be a novel pathway for immunotherapy. We will utilize mouse models to study how targeting peritoneal macrophages can be utilized as an innovative form of immunotherapy, which promises to greatly improve outcomes and survival.