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

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.

• Authors: Sattva S Neelapu, Larry W Kwak, Carol B Kobrin, Craig W Reynolds, John E 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
• Journal: Nature medicine (Nat Med) Vol. 11 Issue 9 Pg. 986-91 (Sep 2005) ISSN: 1078-8956 [Print] United States
• PMID: 16116429 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antineoplastic Agents
• Cancer Vaccines
• Immunoglobulin Idiotypes

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• B-Lymphocytes (physiology)
• Cancer Vaccines
• Female
• Humans
• Immunoglobulin Idiotypes (immunology)
• Lymphoma, Mantle-Cell (drug therapy, immunology)
• Male
• Middle Aged
• T-Lymphocytes (immunology)