Wiskott-Aldrich syndrome protein deficiency in natural killer and dendritic cells affects antitumor immunity.

[wiskott-aldrich syndrome]

Wiskott-Aldrich syndrome (WAS ) is a primary immunodeficiency caused by reduced or absent expression of the WAS protein (WASP ). WAS patients are affected by microthrombocytopenia , recurrent infections , eczema , autoimmune diseases , and malignancies . Although immune deficiency has been proposed to play a role in tumor pathogenesis , there is little evidence on the correlation between immune cell defects and tumor susceptibility . Taking advantage of a tumor -prone model , we show that the lack of WASP induces early tumor onset because of defective immune surveillance . Consistently , the B 16 melanoma model shows that tumor growth and the number of lung metastases are increased in the absence of WASP . We then investigated the in vivo contribution of Was (-/-) NK cells and DCs in controlling B 16 melanoma development . We found fewer B 16 metastases developed in the lungs of Was (-/-) mice that had received WT NK cells as compared with mice bearing Was (-/-) NK cells . Furthermore , we demonstrated that Was (-/-) DCs were less efficient in inducing NK-cell activation in vitro and in vivo . In summary , for the first time , we demonstrate in in vivo models that WASP deficiency affects resistance to tumor and causes impairment in the antitumor capacity of NK cells and DCs .

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wiskott-aldrich syndrome

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