MCPyV immunity: T cells, B cells & clinical significance

University Of Washington, Seattle WA

Investigators

Linked publications & trials

Abstract

Summary- Project 3 Merkel cell carcinoma is a rare and deadly skin cancer that usually results from expression of Merkel cell polyomavirus-derived oncoproteins called T-antigens. The expression of theses viral-derived oncoproteins generates a detectable T-antigen-specific immune response that is typically absent in people that do not have this form of Merkel cell carcinoma. Because the T-antigens are small and exhibit little variation from case-to- case, this allows for a direct comparison of immune responses across all patients with T-antigen-driven “virus- positive” Merkel cell carcinoma. In the previous funding period, we developed approaches to analyze T cell and B cell immune responses specific for the T-antigen oncoproteins. These analyses of T-antigen-specific immune responses have begun to reveal links between the quality and quantity of immune responses and Merkel cell carcinoma progression after treatment. Here, we have put together a strong team of immunologists, virologists, and clinicians to dissect T- Ag-specific immune responses and use a newly developed mouse model of Merkel cell carcinoma to probe mechanisms by which immune cells could control tumor growth. The underlying premise of this study is that analyzing T-antigen-specific B cell and T cell responses in patients with Merkel cell carcinoma using powerful new approaches will predict disease progression because both cell types can contribute to tumor control. With high predictive power, these assessments would indicate candidates in which more aggressive therapies should be initiated before evidence of Merkel cell carcinoma progression is detected. These assessments would also identify individuals where aggressive approaches are not necessary, thereby avoiding the toxicities and high costs of these therapies. Additionally, a long-term objective of our work is to reveal mechanisms of immune control of Merkel cell carcinoma so that new generations of immunotherapies can be developed for individuals who do not generate optimal anti-tumor responses capable of preventing disease progression.