TY - JOUR
T1 - Wiskott-Aldrich syndrome protein deficiency in natural killer and dendritic cells affects antitumor immunity
AU - Catucci, Marco
AU - Zanoni, Ivan
AU - Draghici, Elena
AU - Bosticardo, Marita
AU - Castiello, Maria C.
AU - Venturini, Massimo
AU - Cesana, Daniela
AU - Montini, Eugenio
AU - Ponzoni, Maurilio
AU - Granucci, Francesca
AU - Villa, Anna
PY - 2014
Y1 - 2014
N2 - 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 B16 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 B16 melanoma development. We found fewer B16 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.
AB - 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 B16 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 B16 melanoma development. We found fewer B16 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.
KW - Antitumor immunity
KW - DCs
KW - Immune surveillance
KW - NK cells
KW - Wiskott-Aldrich syndrome
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UR - http://www.scopus.com/inward/citedby.url?scp=84898006391&partnerID=8YFLogxK
U2 - 10.1002/eji.201343935
DO - 10.1002/eji.201343935
M3 - Article
C2 - 24338698
AN - SCOPUS:84898006391
VL - 44
SP - 1039
EP - 1045
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 4
ER -