Abstracts (complete list) - Wissenschaft Online

Ines Gütgemann, Jasmin Teresa Ney, Qi Zhou, Christian Kurts, Hubert Schorle,
Andreas Limmer, Martina Berg, Reinhard Büttner
A novel model of antigen recognition in a hepatic tumor
microenvironment: c-myc/OVA x LAPtTA transgenic mice
Murine hepatic tumor models to investigate antigen presentation and antigen specific Tcell
recognition are hampered either by the lack of a defined cognate antigen or by the
need to inject tumor cells leading to an artificial change of the local host immune
response. Here, we report the generation of a novel conditional mouse model system of
hepatocellular carcinoma (HCC), in which liver specific antigen presentation and
recognition can be followed. When c-myc/OVA transgenic mice expressing chicken
ovalbumin (OVA) and the proto-oncogene c-myc are crossed with liver specific inducer
mice (LAP tTA), the resulting mice (c-myc/OVA x LAPtTA) develop doxicycline
dependent multinodular tumors, resembling human HCC. Although efficient antigen
presentation by intratumoral dendritic cells occurs, the antigen specific T-cell response
is inefficient: Transferred OVA specific OT1 T-cells are rapidly activated, proliferate and
accumulate in the liver and slightly delayed, in systemic immune organs. However,
these CD8+ T-cells show a partial downregulation of the T-cell receptor and lack
Interferon gamma production indicating T-cell tolerance. This model will be useful in
dissecting antigen-specific and non-specific immune responses during different stages of
hepatocarcinogenesis and testing of immune modulatory strategies within an organ
specific tumor microenvironment.