Dear Colleagues,

Metastasis is the main driver of mortality in cancer patients, and the liver is the most common site of metastasis for the majority of solid malignancies. Thus, an effective therapeutic strategy for liver metastasis will likely lead to improved outcomes of stage IV cancer patients and should be prioritized in oncology. As the largest internal organ in the body, the liver maintains essential metabolic, hematopoietic, and immunologic functions that impact human development and physiology. Despite being an area of active research, however, the biological underpinning of the liver’s permissive response to tumor invasion and its subsequent consequences to the host remain poorly understood. An emerging observation in the era of modern cancer immunotherapy is that liver metastasis appears to have a potent deleterious effect on antitumor immunity, with apparent hepatic and systemic changes in immune cell subsets resulting from liver tumor involvement. In melanoma, lung, and urinary cancers, checkpoint inhibitors (CPIs) reverse T cell dysfunction in the tumor microenvironment and facilitate tumor eradication. In the setting of liver metastasis, this process appears inhibited and they are associated with a significantly lower rate of response. Patients who have disease progression despite treatment have a dismal survival rate and we currently lack salvage strategies for CPI refractory disease. Understanding the mechanism of resistance and systemic impact of liver metastasis will enable more effective treatments of this problem. This special issue welcomes articles addressing the cellular and molecular mechanisms driving liver metastasis associated cancer immunotherapy resistance as well as strategies to overcome them.

Dr. James C. Lee and Prof. Dr. Adil Daud

Guest Editors