Nature Medicine
11, 986 - 991 (2005)
Published online: 21 August 2005; | doi:10.1038/nm1290
Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphomaSattva S Neelapu1, 5, Larry W Kwak1, 5, Carol B Kobrin2, Craig W Reynolds3, John E Janik1, Kieron Dunleavy1, Therese White1, Linda Harvey2, Robin Pennington2, Maryalice Stetler-Stevenson1, Elaine S Jaffe1, Seth M Steinberg4, Ronald Gress1, Fran Hakim1
& Wyndham H Wilson11
Experimental and Transplantation Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland
20892, USA. 2
SAIC, NCI-Frederick, 1050 Boyles Street, Frederick, Maryland
21702, USA
3
Office of Scientific Operations, NCI-Frederick, 1050 Boyles Street, Frederick, Maryland
21702, USA. 4
Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland
20892, USA. 5
Present address: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 429, Houston, Texas
77030, USA.
Correspondence should be addressed to Larry W Kwak lkwak@mdanderson.org 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 tolerance1,
2,
3,
4, results from others suggest that B cells are necessary for priming as well as generation of T-cell memory5,
6,
7. 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.
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