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

Nat Med. 2005 Sep;11(9):986-91. doi: 10.1038/nm1290. Epub 2005 Aug 21.

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.

Publication types

  • Clinical Trial

MeSH terms

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

Substances

  • Antineoplastic Agents
  • Cancer Vaccines
  • Immunoglobulin Idiotypes