Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma
- 21 August 2005
- journal article
- clinical trial
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 11 (9), 986-991
- https://doi.org/10.1038/nm1290
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 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.Keywords
This publication has 28 references indexed in Scilit:
- Human Autologous Tumor-Specific T-Cell Responses Induced by Liposomal Delivery of a Lymphoma AntigenClinical Cancer Research, 2004
- Antigen-induced regulatory T cellsBlood, 2004
- Development of effective immunotherapy for the treatment of patients with cancerJournal of the American College of Surgeons, 2004
- Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeysTransplant Immunology, 2003
- Highly effective treatment of acquired immunodeficiency syndrome–related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biologyBlood, 2003
- Effective B Cell Depletion with Rituximab in the Treatment of Autoimmune DiseasesImmunobiology, 2002
- Natural selection of tumor variants in the generation of “tumor escape” phenotypesNature Immunology, 2002
- Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patientsBlood, 2002
- Induction of Immune Responses in Patients with B-Cell Lymphoma against the Surface-Immunoglobulin Idiotype Expressed by Their TumorsThe New England Journal of Medicine, 1992
- Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens.The Journal of Experimental Medicine, 1992