The ubiquitin E3 ligase Cbl-b in T cells tolerance and tumor immunity.
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 hematopoietic 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, chronic viral infections, or cancer.
Loeser
Stefanie
S
IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria. stefanie.loeser@imba.oeaw.ac.at
Penninger
Josef M
JM
D000818:Animals; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D050721:Proto-Oncogene Proteins c-cbl / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*
D050721:Proto-Oncogene Proteins c-cbl