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. In the past year we were able to complete a study showing how the gut microbiome controls bile acids in the gut, which in turn after absorption into the portal vein control accumulation of NKT cells in the liver. These cells control tumor growth in several animal models.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011345-09
Application #
9779871
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Ma, Chi; Han, Miaojun; Heinrich, Bernd et al. (2018) Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science 360:
Eggert, Tobias; Greten, Tim F (2017) Tumor regulation of the tissue environment in the liver. Pharmacol Ther 173:47-57
Eggert, Tobias; Wolter, Katharina; Ji, Juling et al. (2016) Distinct Functions of Senescence-Associated Immune Responses in Liver Tumor Surveillance and Tumor Progression. Cancer Cell 30:533-547
Ma, Chi; Kesarwala, Aparna H; Eggert, Tobias et al. (2016) NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis. Nature 531:253-7
Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba et al. (2015) Tumor-induced CD11b(+) Gr-1(+) myeloid-derived suppressor cells exacerbate immune-mediated hepatitis in mice in a CD40-dependent manner. Eur J Immunol 45:1148-58
Gamrekelashvili, Jaba; Greten, Tim F; Korangy, Firouzeh (2015) Immunogenicity of necrotic cell death. Cell Mol Life Sci 72:273-83
Medina-Echeverz, José; Eggert, Tobias; Han, Miaojun et al. (2015) Hepatic myeloid-derived suppressor cells in cancer. Cancer Immunol Immunother 64:931-40
Ji, Juling; Eggert, Tobias; Budhu, Anuradha et al. (2015) Hepatic stellate cell and monocyte interaction contributes to poor prognosis in hepatocellular carcinoma. Hepatology 62:481-95
Medina-Echeverz, José; Ma, Chi; Duffy, Austin G et al. (2015) Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage. Cancer Immunol Res 3:557-66
Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar et al. (2014) Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage. PLoS One 9:e112717

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