Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer.
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.
['Hegde|Samarth|S|', 'Krisnawan|Varintra E|VE|', 'Herzog|Brett H|BH|', 'Zuo|Chong|C|', 'Breden|Marcus A|MA|', 'Knolhoff|Brett L|BL|', 'Hogg|Graham D|GD|', 'Tang|Jack P|JP|', 'Baer|John M|JM|', 'Mpoy|Cedric|C|', 'Lee|Kyung Bae|KB|', 'Alexander|Katherine A|KA|', 'Rogers|Buck E|BE|', 'Murphy|Kenneth M|KM|', 'Hawkins|William G|WG|', 'Fields|Ryan C|RC|', 'DeSelm|Carl J|CJ|', 'Schwarz|Julie K|JK|', 'DeNardo|David G|DG|']
D000077192:Adenocarcinoma of Lung D000818:Animals D015496:CD4-Positive T-Lymphocytes D018414:CD8-Positive T-Lymphocytes D021441:Carcinoma, Pancreatic Ductal D045744:Cell Line, Tumor D003713:Dendritic Cells D006801:Humans D007167:Immunotherapy D008175:Lung Neoplasms D051379:Mice D008810:Mice, Inbred C57BL D008817:Mice, Mutant Strains D008822:Mice, Transgenic D010190:Pancreatic Neoplasms
dendritic cell immune surveillance pancreatic cancer neoantigen radiation therapy CD40 Flt3L immunotherapy vaccination