B cell subsets are associated with durable responses in distinct cancer types after immune checkpoint inhibition
B cells are a critical arm of the adaptive immune system. However, the impact of B cells and antibody responses on overall cancer survival remains understudied. Here, we report results from a prospective randomized phase 2 trial of 106 patients treated with immune checkpoint inhibitors (ICIs) and identify that B cell antibody responses are associated with exceptional complete responses to ICI in certain cancer types. To further dissect the impact of B cell subtypes, we generated a comprehensive single-cell RNA sequencing database of intratumoral B cells in 12 tumor types from 152 patients. We found a context-dependent role for B cells, in which they are beneficial in certain cancer types and potentially unfavorable in others, with germinal center and memory B cells enriched in favorable prognosis cohorts and immunoglobulin A-positive plasma cells enriched in unfavorable prognosis cohorts. Depletion of B cells using rituximab in patients before surgery affected intratumoral T cell frequency and diversity. Furthermore, we show that B cells improve long-term overall survival even when T cell infiltrates are already high, indicating that a coordinated dual-arm T cell and B cell adaptive immune response is key to long-term tumor control. Overall, these results demonstrate that B cells and antibody responses in the proper context play an important role in durable complete responses in multiple tumor types.
Authors
- Ezra E.W. Cohen (ORCID: https://orcid.org/0000-0002-9872-6242)
- Arno James Mundt (ORCID: https://orcid.org/0000-0001-8457-3698)
- Jason Keith Sicklick (ORCID: https://orcid.org/0000-0003-4403-0271)
- Elizabeth Weihe (ORCID: https://orcid.org/0000-0002-3667-7609)
- Joseph A. Califano (ORCID: https://orcid.org/0000-0002-4715-6761)
- Christopher J. Kane (ORCID: https://orcid.org/0000-0002-8769-2112)
- Jamillah Murtadha (ORCID: https://orcid.org/0009-0007-1186-4217)
- Hitendra Patel (ORCID: https://orcid.org/0000-0002-1687-0727)
- Christina A. M. Jamieson (ORCID: https://orcid.org/0000-0001-5328-2628)
- Jorge Silvio Gutkind (ORCID: https://orcid.org/0000-0002-5150-4482)
- Kathryn Ann Gold (ORCID: https://orcid.org/0000-0001-5165-4424)
- Jingjing Zou (ORCID: https://orcid.org/0000-0002-4749-105X)
- Sayuri Miyauchi (ORCID: https://orcid.org/0009-0000-8439-7751)
- Sangwoo S. Kim (ORCID: https://orcid.org/0009-0003-3746-3199)
- Loren K. Mell (ORCID: https://orcid.org/0000-0003-2277-6080)
- Rebecca Arielle Shatsky (ORCID: https://orcid.org/0000-0003-2289-6234)
- Gregory P. Botta (ORCID: https://orcid.org/0000-0001-9606-4508)
- P. Dominick Sanders
- Razelle Kurzrock (ORCID: https://orcid.org/0000-0003-4110-1214)
- Susan M. Kaech (ORCID: https://orcid.org/0000-0003-1674-1420)
- Andrew B. Sharabi (ORCID: https://orcid.org/0000-0003-2075-1197)
- Natalie E. Quach (ORCID: https://orcid.org/0000-0001-9382-5826)
- James Don Murphy (ORCID: https://orcid.org/0000-0002-0523-9091)
- Sandip Pravin Patel (ORCID: https://orcid.org/0000-0002-8387-4840)
- Karen S. Messer (ORCID: https://orcid.org/0000-0002-9298-2413)
- Roy S (ORCID: https://orcid.org/0000-0002-0411-1221)
- Sarah G Boles (ORCID: https://orcid.org/0000-0002-9956-4767)
- Minya Pu (ORCID: https://orcid.org/0009-0005-3908-4760)
- Lin Zhang (ORCID: https://orcid.org/0000-0002-3767-0249)
- Stephen T. Ryan (ORCID: https://orcid.org/0000-0001-8203-4172)
- Riley N. Jones (ORCID: https://orcid.org/0000-0002-8942-4699)
- Emily I. Pittman
- Shumei Kato (ORCID: https://orcid.org/0000-0003-1193-1815)
- Diane Simeone
Institutions
- Salk Institute for Biological Studies (US)
- Medical College of Wisconsin (US)
- University of California San Diego (US)
- Moores Cancer Center (US)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2026-10-28
- DOI
- https://doi.org/10.1126/scitranslmed.adv7928
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Varian Medical Systems
- National Institutes of Health