| First Author | Tzeng A | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 10 | Pages | 2503-2511 |
| PubMed ID | 27926855 | Mgi Jnum | J:241678 |
| Mgi Id | MGI:5903363 | Doi | 10.1016/j.celrep.2016.11.020 |
| Citation | Tzeng A, et al. (2016) Temporally Programmed CD8alpha+ DC Activation Enhances Combination Cancer Immunotherapy. Cell Rep 17(10):2503-2511 |
| abstractText | 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-alpha (IFNalpha) 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 IFNalpha-induced activation of cross-presenting CD8alpha+ 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 programming DC activation to occur after tumoricidal activity enhanced tumor control by multiple distinct combination immunotherapies, highlighting dose schedule as an underappreciated factor that can profoundly affect the success of multi-component immunotherapies. |
