B cells specific for polyomavirus-derived oncoprotein are predictive of Merkel cell carcinoma progression

Merkel cell carcinoma usually results from integration of an oncogenic version of the Merkel cell polyomavirus T-antigen. While T-antigen-specific antibodies are produced by most patients with T-antigen-driven MCC and are used to monitor disease recurrence, baseline antibody titers do not associate with MCC outcome. Here, we analyzed the frequency and phenotype of T-antigen-specific and total B cells from MCC patient blood and tumor samples in search of predictive biomarkers of disease outcome. While no blood-associated B cell phenotypes were strongly associated with disease outcome, the presence of detectable T-antigen-specific antibody-secreting and/or germinal center B cells in MCC patient tumor samples accurately predicted disease control. In vitro, B cells engineered to be specific for T-antigen were capable of robust activation T-antigen-specific CD4+ T cells. Together, these results show the predictive power of B cell responses in relation to MCC outcomes and may suggest that cancer-specific B cells enhance anti-tumor immunity. Count matrices and B cell receptor sequences from single cell RNA sequencing data are included for immune and tumor cells found in Merkel cell carcinoma patient tumors *************************************************************** Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access. ***************************************************************