title: 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.affiliation: Experimental and Transplantation Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.forename: Carol B
authors.initials: CB
authors.lastname: Kobrin
authors.forename: Craig W
authors.initials: CW
authors.lastname: Reynolds
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.forename: Kieron
authors.initials: K
authors.lastname: Dunleavy
authors.forename: Therese
authors.initials: T
authors.lastname: White
authors.forename: Linda
authors.initials: L
authors.lastname: Harvey
authors.forename: Robin
authors.initials: R
authors.lastname: Pennington
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Ronald
authors.initials: R
authors.lastname: Gress
authors.forename: Fran
authors.initials: F
authors.lastname: Hakim
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000502:physiology*; D019496:Cancer Vaccines; D005260:Female; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes