title: AIDing cancer treatment: Reducing AID activity via HSP90 inhibition.
abstract: The activation induced deaminase (AID) catalyses the two key events underlying humoral adaptive immunity: class switch recombination and somatic hypermutation of antibody genes in B lymphocytes. AID accomplishes this task by directly deaminating cytosines within the genomic immunoglobulin locus, thereby triggering a complex mutagenic process eventually leading to improved effector function of antibodies. However, it has long been noticed that AID can be aberrantly expressed in cancer and that its activity is not absolutely restricted to antibody genes, as substantial genome-wide off-target mutations have been observed, which contribute to tumorigenesis and clonal evolution of AID-expressing malignancies. In this issue of the European Journal of Immunology, Montamat-Sicotte et al. [Eur. J. Immunol. 2015. 45: 2365-2376] investigate the feasibility and efficacy of in vivo inhibition of AID with HSP90 inhibitors in a mouse model of B-cell leukemia and in vitro with a human breast cancer cell line, thereby demonstrating that cancer patients may benefit from preventing noncanonical AID functions.
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, 3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rebhandl
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, 3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Geisberger
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D003564:Cytidine Deaminase / Q000276:immunology*; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D009363:Neoplasm Proteins / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D009363:Neoplasm Proteins; D003564:Cytidine Deaminase
keywords: Activation induced deaminase; Antibody response; Class switch recombination; HSP90 inhibitors; Leukemia