Stephanie K. Dougan
Harvard University
85Publications
24H-index
2,174Citations
Publications 85
Newest
Published on Jan 1, 2019in Gastroenterology 20.77
Vinod P. Balachandran12
Estimated H-index: 12
(Memorial Sloan Kettering Cancer Center),
Gregory L. Beatty25
Estimated H-index: 25
(University of Pennsylvania),
Stephanie K. Dougan24
Estimated H-index: 24
(Harvard University)
Abstract Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer in the US by 2025 1 , with 5-year survival at less than 10% 2 . In other recalcitrant cancers, immunotherapy has shown unprecedented response rates, including durable remissions after drug discontinuation. However, responses to immunotherapy in PDAC are rare. Accumulating evidence in mice and humans suggests that this remarkable resistance is linked to the complex, dueling role of the immune syste...
Source Cite
Published on Feb 19, 2018in Cancer immunology research 9.19
Michael Dougan13
Estimated H-index: 13
(Harvard University),
Jessica R. Ingram16
Estimated H-index: 16
(Harvard University)
+ 12 AuthorsMariah M. Servos3
Estimated H-index: 3
(Harvard University)
Cytokine-based therapies for cancer have not achieved widespread clinical success because of inherent toxicities. Treatment for pancreatic cancer is limited by the dense stroma that surrounds tumors and by an immunosuppressive tumor microenvironment. To overcome these barriers, we developed constructs of single-domain antibodies (VHHs) against PD-L1 fused with IL-2 and IFNγ. Targeting cytokine delivery in this manner reduced pancreatic tumor burden by 50%, whereas cytokines fused to an irrelevan...
8 Citations Source Cite
Published on Jul 1, 2018in Immunotherapy 3.46
Stephanie K. Dougan24
Estimated H-index: 24
(Harvard University),
Michael Dougan13
Estimated H-index: 13
(Harvard University)
Inhibition of the T-cell co-inhibitory checkpoint receptors or their ligands CTLA-4, PD-1 and PD-L1 using monoclonal antibodies has proven to be highly effective against many cancers. Yet many cancers remain resistant to checkpoint blockade, and durable remissions occur in only a minority of patients. Novel approaches to enhancing antitumor responses are thus necessary in order to expand the reach of these treatments. The inhibitor of apoptosis (IAP) protein family comprises a diverse group of p...
5 Citations Source Cite
Published on Jan 1, 2018in Cancer immunology research 9.19
Eleanor Clancy-Thompson4
Estimated H-index: 4
(Harvard University),
Lestat Ali3
Estimated H-index: 3
(Harvard University)
+ 5 AuthorsStephanie K. Dougan24
Estimated H-index: 24
(Harvard University)
Inhibitor of apoptosis protein (IAP) antagonists are in clinical trials for a variety of cancers, and mouse models show synergism between IAP antagonists and anti-PD-1 immunotherapy. Although IAP antagonists affect the intrinsic signaling of tumor cells, their most pronounced effects are on immune cells and the generation of antitumor immunity. Here we examined the effects of IAP antagonism on T-cell development using mouse fetal thymic organ culture and observed a selective loss of iNKT cells, ...
2 Citations Source Cite
Published on Sep 7, 2018in Frontiers in Immunology 5.51
Sayeda Yasmin-Karim7
Estimated H-index: 7
(Harvard University),
Patrick Bruck3
Estimated H-index: 3
(Harvard University)
+ 6 AuthorsWilfred Ngwa17
Estimated H-index: 17
(University of Massachusetts Amherst)
Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an in situ vaccine. In practice, this abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a single dose of stereotactic body radiation therapy (SBRT) synergizes with intratumoral injection of agonistic anti-CD40, resulting in regression of non-treated contralateral tumors and formation of l...
1 Citations Source Cite
Published on Nov 7, 2018in Cancer immunology research 9.19
Eleanor Clancy-Thompson4
Estimated H-index: 4
(Harvard University),
C.A. Devlin (Massachusetts Institute of Technology)+ 7 AuthorsStephanie K. Dougan24
Estimated H-index: 24
(Harvard University)
T-cell priming occurs when a naive T cell recognizes cognate peptide–MHC complexes on an activated antigen-presenting cell. The circumstances of this initial priming have ramifications on the fate of the newly primed T cell. Newly primed CD8 + T cells can embark onto different trajectories, with some becoming short-lived effector cells and others adopting a tissue resident or memory cell fate. To determine whether T-cell priming influences the quality of the effector T-cell response to tumors, w...
Source Cite
Published on Sep 14, 2018in The EMBO Journal 10.56
Ying‐Cing Lin (Ragon Institute of MGH, MIT and Harvard), Simone Pecetta5
Estimated H-index: 5
(Ragon Institute of MGH, MIT and Harvard)
+ 9 AuthorsUsha Nair22
Estimated H-index: 22
(Ragon Institute of MGH, MIT and Harvard)
Abstract Here, we describe a one‐step, in vivo CRISPR/Cas9 nuclease‐mediated strategy to generate knock‐in mice. We produced knock‐in (KI) mice wherein a 1.9‐kb DNA fragment bearing a pre‐arranged human B‐cell receptor heavy chain was recombined into the native murine immunoglobulin locus. Our methodology relies on Cas9 nuclease‐induced double‐stranded breaks directed by two sgRNAs to occur within the specific target locus of fertilized oocytes. These double‐stranded breaks are subsequently repa...
Source Cite
Published on Oct 1, 2018in Journal of Experimental Medicine 10.79
Yoshinaga Ito9
Estimated H-index: 9
,
Orr Ashenberg10
Estimated H-index: 10
+ 10 AuthorsLuc Teyton62
Estimated H-index: 62
1 Citations Source Cite
Jessica R. Ingram16
Estimated H-index: 16
(Harvard University),
Olga S. Blomberg4
Estimated H-index: 4
(Boston Children's Hospital)
+ 15 AuthorsStephanie Crowley1
Estimated H-index: 1
(Harvard University)
Ipilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved “checkpoint”-blocking anticancer therapy. In mouse tumor models, the response to antibodies against CTLA-4 depends entirely on expression of the Fcγ receptor (FcγR), which may facilitate antibody-dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade remains unknown. To understand the role of CTLA-4 blockade in the complete absence of Fc-dependent functions, ...
7 Citations Source Cite
123456789