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

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(1-4), results from others suggest that B cells are necessary for priming as well as generation of T- cell memory(5-7). We assessed immune responses to a wellcharacterized 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.