@article{aab6fa4210e84e23af06392cd4a89e1a,
title = "Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer",
abstract = "Here, we utilized spontaneous models of pancreatic and lung cancer to examine how neoantigenicity shapes tumor immunity and progression. As expected, neoantigen expression during lung adenocarcinoma development leads to T cell-mediated immunity and disease restraint. By contrast, neoantigen expression in pancreatic ductal adenocarcinoma (PDAC) results in exacerbation of a fibro-inflammatory microenvironment that drives disease progression and metastasis. Pathogenic TH17 responses are responsible for this neoantigen-induced tumor progression in PDAC. Underlying these divergent T cell responses in pancreas and lung cancer are differences in infiltrating conventional dendritic cells (cDCs). Overcoming cDC deficiency in early-stage PDAC leads to disease restraint, while restoration of cDC function in advanced PDAC restores tumor-restraining immunity and enhances responsiveness to radiation therapy.",
keywords = "CD40, Flt3L, dendritic cell, immune surveillance, immunotherapy, neoantigen, pancreatic cancer, radiation therapy, vaccination",
author = "Samarth Hegde and Krisnawan, {Varintra E.} and Herzog, {Brett H.} and Chong Zuo and Breden, {Marcus A.} and Knolhoff, {Brett L.} and Hogg, {Graham D.} and Tang, {Jack P.} and Baer, {John M.} and Cedric Mpoy and Lee, {Kyung Bae} and Alexander, {Katherine A.} and Rogers, {Buck E.} and Murphy, {Kenneth M.} and Hawkins, {William G.} and Fields, {Ryan C.} and DeSelm, {Carl J.} and Schwarz, {Julie K.} and DeNardo, {David G.}",
note = "Funding Information: S.H. was supported by NCI predoctoral-to-postdoctoral fellowship F99CA223043 . J.K.S. was supported by NCI R01CA181745 , and the Small Animal Radiation Research Platform was purchased with S10OD020136 . D.G.D. was supported by NCI P50CA196510 , R01CA177670 , R01CA203890 , P30CA09184215 , and BJC Cancer Frontier Fund . C.J.D. was supported by 1DP5OD026427 . We thank Brian Ruffell for his feedback while drafting the manuscript. We thank the Genome Technology Access Center for help with genomic analyses, supported by NCI P30CA91842 and by ICTS /CTSA UL1RR024992 from the NCRR and the NIH . We also thank the Digestive Disease Research Core Center for histological help, supported by NIDDK P30DK052574 . Imaging experiments were performed through the use of Washington University Center for Cellular Imaging supported by CDI -CORE-2015-505 and the Foundation for Barnes-Jewish Hospital . Funding Information: S.H. was supported by NCI predoctoral-to-postdoctoral fellowship F99CA223043. J.K.S. was supported by NCI R01CA181745, and the Small Animal Radiation Research Platform was purchased with S10OD020136. D.G.D. was supported by NCI P50CA196510, R01CA177670, R01CA203890, P30CA09184215, and BJC Cancer Frontier Fund. C.J.D. was supported by 1DP5OD026427. We thank Brian Ruffell for his feedback while drafting the manuscript. We thank the Genome Technology Access Center for help with genomic analyses, supported by NCI P30CA91842 and by ICTS/CTSA UL1RR024992 from the NCRR and the NIH. We also thank the Digestive Disease Research Core Center for histological help, supported by NIDDK P30DK052574. Imaging experiments were performed through the use of Washington University Center for Cellular Imaging supported by CDI-CORE-2015-505 and the Foundation for Barnes-Jewish Hospital. Conceptualization, S.H. and D.G.D.; Methodology, S.H. C.J.D. J.K.S. and D.G.D.; Investigation, S.H. V.E.K. B.H.H. C.Z. M.A.B. B.L.K. J.P.T. G.D.H. J.M.B. C.M. K.B.L. and K.A.A.; Writing ? Original Draft, S.H.; Writing ? Review & Editing, S.H. R.C.F. and D.G.D.; Funding, S.H. and D.G.D.; Resources, B.E.R. W.G.H. R.C.F. K.M.M. C.J.D. J.K.S. and D.G.D.; Supervision, D.G.D. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = mar,
day = "16",
doi = "10.1016/j.ccell.2020.02.008",
language = "English",
volume = "37",
pages = "289--307.e9",
journal = "Cancer Cell",
issn = "1535-6108",
number = "3",
}