Temporally Programmed CD8α⁺ DC Activation Enhances Combination Cancer Immunotherapy.

ABSTRACT: Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α⁺ dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response. Due to decreased phagocytic ability post-maturation, DCs activated too early captured less antigen and could not effectively prime CD8⁺ T cells. Temporally progr

SUBMITTER: Tzeng A 

PROVIDER: S-EPMC5204262 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature