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Research in practice: The impact of interferon‐α therapy on immune tolerance
Author(s) -
Raker Verena,
Steinbrink Kerstin
Publication year - 2014
Publication title -
jddg: journal der deutschen dermatologischen gesellschaft
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.463
H-Index - 60
eISSN - 1610-0387
pISSN - 1610-0379
DOI - 10.1111/ddg.12297
Subject(s) - immunology , autoimmunity , melanoma , immune system , adjuvant , immunotherapy , immune tolerance , medicine , interferon gamma , interferon , cancer research , effector , mapk/erk pathway , biology , phosphorylation , microbiology and biotechnology
Summary Interferon‐α (IFN‐α) is the only drug approved for adjuvant therapy of malignant melanoma and is also used in the treatment of hematological and solid tumors. Along with its proven clinical efficacy, IFN‐α produces several side effects, particularly with regard to autoimmune disorders. Curious about symptoms of autoimmunity during IFN‐α therapy, we asked whether IFN‐α directly impacts on immune tolerance. We found that IFN‐α does alter the function of tolerogenic dendritic cells (DC) as well as of induced and naturally occurring T‐regulatory cells (nTregs). IFN‐α blocks the tolerogenic phenotype of DC by inducing maturation and thus preventing the induction of inducible Tregs by DC. It also has direct effects on nTregs. IFN‐α reduces cAMP in Tregs via ERK/phosphodiesterase‐mediated pathways. Since cAMP is essentially involved in suppression by nTregs, the IFN‐α‐dependent reduction of cAMP levels abolishes the suppressive capacity of nTregs. Therefore, Tregs are incapable of suppressing the activity of effector T cells and natural killer cells, resulting in tumor rejection. Thus, IFN‐α overcomes immunological tolerance processes, leading to an improved immunostimulation and efficient tumor rejection, but also increases the risk of autoimmunity.