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Πέμπτη 29 Ιουνίου 2017

Intrinsic and Extrinsic Causes of Malignancies in Primary Immunodeficiency Disorders

Publication date: Available online 29 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Fabian Hauck, Rebecca Voss, Christian Urban, Markus G. Seidel
Malignancies occur with a higher incidence rate and manifest earlier in life in patients with primary immunodeficiency disorders (PID) than in the general population. However, no universal mechanism of malignancy predisposition in PID can been determined. Despite the strong support for the physiological role of tumor immunosurveillance and increasing success of strategies in immunological tumor therapy, which include checkpoint inhibition, monoclonal antibodies, and engineered T cell antigen receptors, the incidence and pattern of malignancies in PID do not reflect an increased tumor immune escape per se. In contrast, malignancies appear to be restricted to either i) tissue types bearing the same molecular defect that underlies the PID such as syndromes of DNA repair deficiency or immune cell-specific maturation or functional defects that suggest a cell-intrinsic oncogenic basis, or ii) other tissues when they are infected by transforming viruses or chronically inflamed, pointing towards extrinsic causes for transformation that are potentially facilitated by but not predominantly owed to a lack of immunosurveillance. Based on recent studies of preexisting conditions in malignancy patients and on malignancies in large PID cohorts, we conclude that a large part of tumor predisposition in PID is derived from the same molecular defect as the immunodeficiency itself. The presented concept elucidates diverse pathomechanisms and risks of malignancies in PID in the light of current tumor immune therapies.



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