Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma

Sattva S. Neelapu, Larry W. Kwak, Carol B. Kobrin, Craig W. Reynolds, John Edward Janik, Kieron Dunleavy, Therese White, Linda Harvey, Robin Pennington, Maryalice Stetler-Stevenson, Elaine S. Jaffe, Seth M. Steinberg, Ronald Gress, Fran Hakim, Wyndham H. Wilson

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91 Scopus citations

Abstract

The role of B cells in T-cell priming is unclear, and the effects of B-cell depletion on immune responses to cancer vaccines are unknown. Although results from some mouse models suggest that B cells may inhibit induction of T cell-dependent immunity by competing with antigen-presenting cells for antigens, skewing T helper response toward a T helper 2 profile and/or inducing T-cell tolerance, results from others suggest that B cells are necessary for priming as well as generation of T-cell memory. We assessed immune responses to a well-characterized idiotype vaccine in individuals with severe B-cell depletion but normal T cells after CD20-specific antibody-based chemotherapy of mantle cell lymphoma in first remission. Humoral antigen- and tumor-specific responses were detectable but delayed, and they correlated with peripheral blood B-cell recovery. In contrast, vigorous CD4+ and CD8+ antitumor type I T-cell cytokine responses were induced in most individuals in the absence of circulating B cells. Analysis of relapsing tumors showed no mutations or change in expression of target antigen to explain escape from therapy. These results show that severe B-cell depletion does not impair T-cell priming in humans. Based on these results, it is justifiable to administer vaccines in the setting of B-cell depletion; however, vaccine boosts after B-cell recovery may be necessary for optimal humoral responses.

Original languageEnglish (US)
Pages (from-to)986-991
Number of pages6
JournalNature Medicine
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 1 2005

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Neelapu, S. S., Kwak, L. W., Kobrin, C. B., Reynolds, C. W., Janik, J. E., Dunleavy, K., ... Wilson, W. H. (2005). Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nature Medicine, 11(9), 986-991. https://doi.org/10.1038/nm1290