Temporally Programmed CD8α[superscrip +] DC Activation Enhances Combination Cancer Immunotherapy
Name
Temporally programmed.pdf
Size
1.62 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Szeto, Gregory L.
Overwijk, Willem W.
Tzeng, Alice
Kauke, Monique Jacqueline
Zhu, Eric Franklin
Moynihan, Kelly Dare
Opel, Cary Francis
Yang, Nicole Jie Yeon
Mehta, Naveen
Irvine, Darrell J
Alternative Title
Temporally Programmed CD8α+ DC Activation Enhances Combination Cancer Immunotherapy
Date Issued
December 2016
Journal
Cell Reports
Publisher
Elsevier
Citation
Tzeng, Alice et al. “Temporally Programmed CD8α+ DC Activation Enhances Combination Cancer Immunotherapy.” Cell Reports 17.10 (2016): 2503–2511.
Version
Final published version
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[superscript +] 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[superscript +] 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.celrep.2016.11.020
