Cancer is the rapid, uncontrollable proliferation of mutated cells that spread within tissue and eventually throughout the body. Cancer types are dependent on the specific tissue in which tumors arise. Therefore, each tumor has various mutations and characteristics and will respond to therapies differently. Some tumors are more accessible while others are in sensitize areas that can only be reached with precision techniques and treatments. The advancement of medicine has tailored cancer therapies to directly target tumor cells with heightened efficacy.
Different cancer treatments have significantly improved healthcare regimens in patients. Specifically, immunotherapy is a type of treatment which redirects the immune system toward the cancer. Ovarian cancer is one tumor type that is significantly reduced with immunotherapy. Various subtypes of ovarian cancer are treated with immunotherapy combined with standard of care, including chemotherapy and/or surgery. Although treatments for ovarian cancer are getting better, over half of the roughly 20,000 women diagnosed in America will die as a result of the disease. Unfortunately, ovarian cancer risk is increased as women age and is one of the leading causes of death. Therefore, it is critical that scientists continue to improve immunotherapies for patients.
A recent article in Science Immunology, by Dr. Lydia Lynch and others, reveal why the immune system is suppressed and how immunotherapies have limited efficacy in ovarian cancer. Specifically, Lynch and her team uncovered how ascites or lipid-rich fluid in the abdomen, weakens the immune response. Lynch is an Associate Professor at the Trinity Biomedical Science Institute in Dublin, Ireland. Her lab’s research focuses on the relationship between immune cells and different metabolic mechanisms that drive systemic responses. Lynch’s work centers around obesity and cancer, investigating the effects of altered metabolism and immune cell function in both pathologies.
Lynch and her team discovered that ascites disrupts immune cell function in patients with ovarian cancer. Two immune cells known as natural killer (NK) cells and T cells become dysregulated and lose their function. During a healthy immune response, NK and T cells are responsible for identifying and eliminating infected or mutated cells. However, the lipids within the ascites change the metabolism in both cell types and limit their efficacy toward the tumor. Additionally, researchers also found that preventing NK and T cell lipid uptake improved their antitumor function. As a result, Lynch and her group hope this mechanism of lipid uptake can be used as a new therapeutic target and improve therapies.
This is a major discovery in the field of ovarian cancer since ascites fluid is a common characteristic which is poorly understood. Previously, many researchers believed that ascites fluid limits cancer therapy, but were unsure how or why. Lynch and her team successfully demonstrated the mechanism of lipid uptake, which can suppress the body’s immune response and generate a therapy-resistant environment around the tumor. This work demonstrates that by targeting lipid-uptake, immune cells can regain their anti-tumor function. As a result, this discovery has the potential to enhance immunotherapy against aggressive disease and improve survival in patients with ovarian cancer.
Article, Science Immunology, Lydia Lynch, Trinity Biomedical Science Institute