T-antigen-specific B cell responses in Merkel cell carcinoma tumors predict disease outcomes

Summary: Abstract Body: Merkel cell carcinoma (MCC) often results from integration of a truncated version of the Merkel cell polyomavirus T-antigen (T-Ag) gene into a host cell chromosome. This gene encodes T-Ag proteins that promote MCC tumorigenesis and are recognized by T & B lymphocytes. While extensive studies have established the importance of T-Ag-specific T cells in anti-MCC immunity, the roles that B cells play in MCC control have not been explored. Using single cell technologies, we analyzed the phenotype and antibodies of T-Ag binding B cells found in 14 MCC-infiltrated lymph nodes. Strikingly, 9/9 patients with tumors that had T-Ag-specific B cells with germinal center (GC) or antibody-secreting (ASC) phenotypes experienced extended progression-free survival, with no MCC progression by 4 years after tumor excision. In contrast, 5/5 patients with MCC-infiltrated lymph nodes that lacked these B cells experienced rapid disease progression by a median of 0.35 years (p<0.0001). Additionally, tumors with T-Ag-specific B cells with GC or ASC phenotypes had higher frequencies of follicular helper CD4+ T compared to tumors without these B cells (median 11% vs 4% out of total CD4+ T cells, p=0.002). These results suggest strong B and T cell synergy in patients with better MCC control. Of note, adverse clinical risk factors present at the time of tumor removal were not significantly different between MCC patients whose tumors had T-Ag-specific GC or ASC B cells and patients with tumors lacking these cells (Fisher’s exact test, p= 0.99). Together, our findings suggest that cancer-specific B cells may promote anti-tumor immunity via increased T cell responses and that approaches to augment cancer-specific B cell function could benefit MCC patients. Haroldo J. Rodriguez Chevez^{1, 2, 3}, Allison J. Remington¹, Rian Alam¹, Macy W. Gilmour¹, Carina Morningstar¹, Thomas Pulliam¹, Joseph Carter², Denise Galloway², Paul Nghiem^{1, 2}, Justin J. Taylor^{3, 2} 1. Dermatology, University of Washington, Seattle, WA, United States. 2. Fred Hutchinson Cancer Center, Seattle, WA, United States. 3. Medicine, University of Virginia, Charlottesville, VA, United States. Adaptive and Auto-Immunity