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Project C2

Identification of Molecular Targets for Immune-Based Therapies in Hepatocellular Carcinoma

Principal Investigators: Dr. T. Wirth


Short Summary

Tumors have evolved mechanisms to evade the host immune response. In the past we have identified various immune suppressor mechanisms in patients with HCC, including an accumulation of CD4+ regulatory T-cells and myeloid derived suppressor cells (MDSCs). For the project presented here, we propose to investigate possible mechanisms that lead to an accumulation of MDSCs in a murine model, which mimics the situation of human HCC tumor growth and development. These studies will ultimately lead to the identification of possible new targets that impair immune suppression mechanisms and support immune-based strategies against HCC.

 

List of relevant publications

    1. Wirth TC, Rai D, Sabel JT, Bair T, Xue HH, Harty JT and Badovinac VP (2010). Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8 T cell differentiation. Immunity, 33(1):128-40
    2. Wirth TC, Harty JT and Badovinac VP (2010). Modulating numbers and phenotype of CD8 T cells in secondary immune responses. Eur J Immunol., 40(7):1916-1926.
    3. Wirth TC, Badovinac VP, Zhao L, Dailey MO, Harty JT (2009). Differentiation of Central Memory CD8 T Cells Is Independent of CD62L-Mediated Trafficking to Lymph Nodes J Immunol., 182(10):6195-206.
    4. Wirth T, Harty JT (2009). Initial TCR transgenic precursor frequency alters functional behaviour of CD8 T cells responding to acute infection. Adv Exp Med Biol 633:71-80.
    5. Wirth TC, Pham NL, Harty JT, Badovinac VP (2009). High initial frequency of TCR-transgenic CD8 T cells alters inflammation and pathogen clearance without affecting memory T cell function. Mol Immunol. 47(1):71-8.
    6. Wirth T, Kühnel F, Fleischmann-Mundt B, Woller N, Djojosubroto M, Rudolph KL, Manns M, Zender L, Kubicka S (2005). Telomerase-dependent virotherapy overcomes resistance of hepatocellular carcinomas against chemotherapy and tumor necrosis factor-related apoptosis-inducing ligand by elimination of Mcl-1. Cancer Res. 2005 Aug 15;65(16):7393-402.
    7. Wirth T, Kühnel F, Kubicka S (2005). Telomerase-dependent gene therapy. Curr Mol Med 5(2):243-51. Review.
    8. Wirth T, Zender L, Schulte B, Mundt B, Plentz R, Rudolph KL, Manns M, Kubicka S, Kühnel F (2003). A telomerase-dependent conditionally replicating adenovirus for selective treatment of cancer. Cancer Res 63(12):3181-8.
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