期刊
JOURNAL FOR IMMUNOTHERAPY OF CANCER
卷 7, 期 -, 页码 -出版社
BMJ PUBLISHING GROUP
DOI: 10.1186/s40425-019-0573-5
关键词
Cytotoxic T cells; Tumor infiltrating lymphocytes; CXCL10; Cancer proliferation; Tumor selectivity; STING agonist; Immune activation
资金
- NIH/NCI [R01 CA178960]
- NIH/NIGMS [T32GM080202]
- Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin
- Bobbie Nick Voss Charitable Foundation
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.\
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