4-1BB-Specific Monoclonal Antibody Promotes the Generation of Tumor-Specific Immune Responses by Direct Activation of CD8 T Cells in a CD40-Dependent Manner

• DOI: 10.4049/jimmunol.169.4.1792
• Publication Date: 2014-04-20T22:19:11Z
• Authors: Robert E Miller; Jon Jones; Tiep Le; James Whitmore; Norman Boiani; Brian Gliniak; David H Lynch
• Keywords: CD137

4-1BB (CD137) is a member of the TNFR superfamily (TNFRSF9). T cell expression restricted to activated cells, and cross-linking has been shown deliver costimulatory signal. Here we have that treatment tumor-bearing mice with agonistic 4-1BB-specific Abs can lead cell-mediated tumor rejection. In vivo mAb depletion experiments demonstrated this rejection requires CD8(+) cells but not CD4(+) or NK cells. Both IFN-gamma- CD40-mediated signals were also required, because no benefit was observed on in which genes for these molecules had knocked out. Interestingly, 4-1BB-mediated stimulation immune responses CD40L(-/-) effective (although at reduced level), may suggest existence an alternative ligand CD40. Additional IL-15(-/-) indicate IL-15 required either generation primary tumor-specific response maintenance memory response. contrast, presence CD4 during appears play significant role antitumor memory. Finally, number dendritic expanded by Fms-like tyrosine kinase3 treatment, effects ligation enhanced.