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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

05/01/2019

Pubmed ID

31036082

Pubmed Central ID

PMC6489306

DOI

10.1186/s40425-019-0573-5

Scopus ID

2-s2.0-85065258266   2 Citations

Abstract

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 MB

Authors

Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Bryon D. Johnson PhD Professor in the Medicine department at Medical College of Wisconsin
Matthew J. Riese MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Emily Vonderhaar in the CTSI department at Medical College of Wisconsin - CTSI




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