We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Suppressive myeloid cells are expanded by biliary tract cancer-derived cytokines in vitro and associate with aggressive disease.
- Authors
Ware, Michael B.; Zaidi, Mohammad Y.; Yang, Jennifer; Turgeon, Michael K.; Krasinskas, Alyssa; Mace, Thomas A.; Keenan, Kaitlin; Farren, Matthew R.; Ruggieri, Amanda N.; Li, Yiman; Zhang, Chao; Chen, Zhengjia; Young, Gregory S.; Elnaggar, Omar; Che, Zheng; Maithel, Shishir K.; Bekaii-Saab, Tanios; El-Rayes, Bassel; Lesinski, Gregory B.
- Abstract
<bold>Background: </bold>BTC is an aggressive disease exacerbated by inflammation and immune suppression. Expansion of immunosuppressive cells occurs in biliary tract cancer (BTC), yet the role of BTC-derived cytokines in this process is unclear.<bold>Methods: </bold>Activated signalling pathways and cytokine production were evaluated in a panel of human BTC cell lines. Human peripheral blood mononuclear cells (PBMCs) were cultured with BTC supernatants, with and without cytokine neutralising antibodies, and analysed by flow cytometry or immunoblot. A human BTC tissue microarray (TMA, n = 69) was stained for IL-6, GM-CSF, and CD33+S100a9+ cells and correlated with clinical outcomes.<bold>Results: </bold>Immunomodulatory factors (IL-6, GM-CSF, MCP-1) were present in BTC supernatants. BTC supernatants expanded CD33dimCD11b+HLA-DRlow/- myeloid-derived suppressor cells (MDSCs) from human PBMCs. Neutralisation of IL-6 and GM-CSF in BTC supernatants inhibited activation of STAT3/5, respectively, in PBMCs, with heterogeneous effects on MDSC expansion in vitro. Staining of a BTC TMA revealed a positive correlation between IL-6 and GM-CSF, with each cytokine and more CD33+S100a9+ cells. Increased CD33+S100a9+ staining positively correlated with higher tumour grade, differentiation and the presence of satellite lesions.<bold>Conclusion: </bold>BTC-derived factors promote suppressive myeloid cell expansion, and higher numbers of CD33+S100a9+ cells in resectable BTC tumours correlates with more aggressive disease.
- Subjects
CYTOKINES; RESEARCH; BILE duct tumors; CELL culture; CULTURE media (Biology); CANCER invasiveness; CYTOMETRY; RESEARCH methodology; CELL physiology; IMMUNOLOGY technique; EVALUATION research; COMPARATIVE studies; RESEARCH funding; MYELOID cells; CALCIUM-binding proteins; ANTIGENS; TUMOR grading
- Publication
British Journal of Cancer, 2020, Vol 123, Issue 9, p1377
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-020-1018-0