Mechanisms of liver metastasis and associated resistance to immunotherapy

Melanoma is an aggressive form of skin cancer that frequently spreads (metastasizes) to other organs. While some patients with metastatic melanoma benefit from novel drug therapies, such as immunotherapies, which reinvigorate the body's own immune system to detect and eliminate cancer cells, most patients do not. Interestingly, patients who have metastasis to the liver are significantly less likely to respond to immunotherapies, and the underlying reasons are unclear. Here, we established a melanoma mouse model that, similar to patients, experiences liver metastasis, and therefore enabling us to study the impact of these lesions on responses to immunotherapies. We use cutting-edge methods, such as genome-editing tools and high-resolution molecular profiling and imaging methods to dissect both how liver metastases develop and how they impact the immune system in the entire body. The ultimate goal of this work is to develop improved therapies for melanoma patients with metastases to the liver.