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Review

The Ubiquitin E3 Ligase Cbl-b in T Cells Tolerance and Tumor Immunity

Stefanie Loeser and Josef M. Penninger

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The implication of the immune system in tumor surveillance is proven and widely accepted. However, anti-cancer immunotherapy is still difficult due to insufficient activation, immune suppression and tolerance induction. The ubiquitin E3 ligase Cbl-b, is a member of the Cbl (Casitas B-lineage Lymphoma) protein family and was identified as a key dominant “tolerogenic” factor in T cells that directly regulates T-cell activation by controlling activation thresholds and the requirement for co-stimulation. Intriguingly, Cbl-b deficient mice spontaneously reject a variety of cancers including spontaneous solid tumors and hematopietic malignancies. Mechanistically, modulation of Cbl-b in T cells controls activation of tumor-reactive cytotoxic T cells in vivo and might circumvent several limitations of T cell immunotherapy. Therefore manipulation of Cbl-b might provide us with a unique opportunity for future immune treatment of human disorders such as autoimmunity, chronical viral infections, or cancer.

Authors

Stefanie Loeser

Institute of Molecular Biotechnology of the Austrian Academy of Sciences; Vienna, Austria

Josef M. Penninger

Institute of Molecular Biotechnology, Austrian Academy of Sciences

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.