Abstract

It has been shown that tumors have developed numerous ways to escape tumor specific immune responses. These mechanisms will ultimately not only enhance tumor growth, but also impair the effect of immune based therapies in cancer. Myeloid derived suppressor cells represent a recently identified cell population, which has been shown to impair tumor specific immune responses both in mice and human. We have been able to identify a human counterpart of the initially only in mice described MDSC, which is characterized by the expression of CD14 and low/no levels of HLA-DR. We have tested different staining and isolation methods to determine relative and absolute MDSC frequencies in patients with cancer of the GI-tract.Currently we are studying different mechanism of how to deplete MDSC in patients with cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011344-06
Application #
9153874
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Greten, Tim F; Eggert, Tobias (2017) Cellular senescence associated immune responses in liver cancer. Hepat Oncol 4:123-127
Duffy, Austin G; Ulahannan, Susanna V; Makorova-Rusher, Oxana et al. (2017) Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol 66:545-551
Duffy, A G; Greten, T F (2014) Immunological off-target effects of standard treatments in gastrointestinal cancers. Ann Oncol 25:24-32
Duffy, Austin; Zhao, Fei; Haile, Lydia et al. (2013) Comparative analysis of monocytic and granulocytic myeloid-derived suppressor cell subsets in patients with gastrointestinal malignancies. Cancer Immunol Immunother 62:299-307
Greten, Tim F; Zhao, Fei; Gamrekelashvili, Jaba et al. (2012) Human Th17 cells in patients with cancer: Friends or foe? Oncoimmunology 1:1438-1439
Zhao, Fei; Hoechst, Bastian; Gamrekelashvili, Jaba et al. (2012) Human CCR4+ CCR6+ Th17 cells suppress autologous CD8+ T cell responses. J Immunol 188:6055-62
Zhao, Fei; Korangy, Firouzeh; Greten, Tim F (2012) Cellular immune suppressor mechanisms in patients with hepatocellular carcinoma. Dig Dis 30:477-82
Zhao, Fei; Hoechst, Bastian; Duffy, Austin et al. (2012) S100A9 a new marker for monocytic human myeloid-derived suppressor cells. Immunology 136:176-83
Greten, Tim F; Manns, Michael P; Korangy, Firouzeh (2011) Myeloid derived suppressor cells in human diseases. Int Immunopharmacol 11:802-7
Hoechst, Bastian; Gamrekelashvili, Jaba; Manns, Michael P et al. (2011) Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells. Blood 117:6532-41