Response of B cells specific for polyomavirus-derived oncoprotein is predictive of Merkel cell carcinoma tumor control
Merkel cell carcinomas (MCC) typically arise from clonal integration of the Merkel cell polyomavirus. Immunogenic viral oncoproteins then lead to tumorigenesis. Oncoprotein-specific T cells are essential for anti-MCC immunity, but it is unclear whether B cells promote tumor control. Here, we analyzed the frequency and phenotype of viral oncoprotein-specific and total B cells in blood samples from 47 patients with MCC and tumor samples from another 19 patients with MCC. The phenotype of blood B cells did not correlate with MCC patient outcomes. In contrast, all 11 patients with robust oncoprotein-specific antibody-secreting and/or germinal center B cells in tumors experienced long-term MCC control. In vitro, B cells engineered to be specific for viral oncoproteins increased the sensitivity of oncoprotein-specific CD4+ T cells by over 50-fold. Together, our findings suggest that cancer-specific B cells promote antitumor immunity via increased responses by T cells and that cancer-specific augmentation of B cells could be therapeutically relevant.
Authors
- Joseph J. Carter (ORCID: https://orcid.org/0000-0001-6825-1453)
- Kimberly S. Smythe (ORCID: https://orcid.org/0000-0002-2329-8298)
- Ata S. Moshiri (ORCID: https://orcid.org/0000-0001-6684-4503)
- Marti R. Tooley (ORCID: https://orcid.org/0000-0002-8301-0866)
- Katrina Poljakov
- Kristin Robinson
- Rima M. Kulikauskas (ORCID: https://orcid.org/0000-0003-1092-1594)
- Naina Singhi (ORCID: https://orcid.org/0000-0001-8431-1823)
- Allison Schwartz
- Mikel Ruterbusch (ORCID: https://orcid.org/0000-0002-6619-1175)
- Justin J. Taylor (ORCID: https://orcid.org/0000-0001-9718-2901)
- Francesca Urselli
- Erin McClure (ORCID: https://orcid.org/0000-0002-6604-1273)
- Rian Alam
- Anne M. Macy (ORCID: https://orcid.org/0000-0003-4508-3658)
- Blair L. DeBuysscher
- Pulliam Tj
- Carina D. Morningstar
- Melissa L. Baker (ORCID: https://orcid.org/0000-0003-4042-0707)
- Joshua Veatch (ORCID: https://orcid.org/0000-0002-6543-9255)
- Kayla Hopwo (ORCID: https://orcid.org/0000-0001-5590-4224)
- Kristen R Shimp
- Neha Singh (ORCID: https://orcid.org/0000-0002-9654-9000)
- Jakob Bakhtiari
- Logan J. Mullen
- Macy W. Gilmour
- Allison J. Remington
- Maria Iuliano
- Scotia Ouellette
- MingGang Lin
- Cecilia C.S. Yeung
- Gabriel F. Alencar
- Paul Nghiem
- Carolyn Shasha
- Haroldo J. Rodriguez Chevez
- Denise A. Galloway
- David M. Koelle
Institutions
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Johns Hopkins University (US)
- University of Washington (US)
- Johns Hopkins Medicine (US)
- Fred Hutch Cancer Center (US)
- University of Washington Applied Physics Laboratory (US)
- Johns Hopkins Hospital (US)
- University of Virginia (US)
- New York University (US)
- Seattle University (US)
Publication Details
- Journal
- Cancer Immunology Research
- Published
- 2026-03-04
- DOI
- https://doi.org/10.1158/2326-6066.cir-25-0950
- Primary Topic
- Polyomavirus and related diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00