STING agonist inflames the pancreatic cancer immune microenvironment and reduces tumor burden in mouse models. J Immunother Cancer 2019 Apr 29;7(1):115
Date
05/01/2019Pubmed ID
31036082Pubmed Central ID
PMC6489306DOI
10.1186/s40425-019-0573-5Scopus ID
2-s2.0-85065258266 (requires institutional sign-in at Scopus site) 119 CitationsAbstract
Pancreatic cancer is characterized by an immune suppressive stromal reaction that creates a barrier to therapy. A murine transgenic pancreatic cancer cell line that recapitulates human disease was used to test whether a STimulator of Interferon Genes (STING) agonist could reignite immunologically inert pancreatic tumors. STING agonist treatment potently changed the tumor architecture, altered the immune profile, and increased the survival of tumor-bearing mice. Notably, STING agonist increased numbers and activity of cytotoxic T cells within tumors and decreased levels of suppressive regulatory T cells. Further, STING agonist treatment upregulated costimulatory molecule expression on cross-presenting dendritic cells and reprogrammed immune-suppressive macrophages into immune-activating subtypes. STING agonist promoted the coordinated and differential cytokine production by dendritic cells, macrophages, and pancreatic cancer cells. Cumulatively, these data demonstrate that pancreatic cancer progression is potently inhibited by STING agonist, which reignited immunologically cold pancreatic tumors to promote trafficking and activation of tumor-killing T cells.
Author List
Jing W, McAllister D, Vonderhaar EP, Palen K, Riese MJ, Gershan J, Johnson BD, Dwinell MBAuthors
Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of WisconsinBryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Emily Vonderhaar in the CTSI department at Medical College of Wisconsin - CTSI
MESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Cell Line, Tumor
Dendritic Cells
Disease Models, Animal
Female
Homeodomain Proteins
Humans
Lymphocytes, Tumor-Infiltrating
Macrophages
Male
Membrane Proteins
Mice
Mice, Knockout
Pancreatic Neoplasms
T-Lymphocytes, Cytotoxic
Tumor Burden
Tumor Escape
Tumor Microenvironment
Xanthones
