PuSH - Publikationsserver des Helmholtz Zentrums München

Belting, L. ; Hömberg, N. ; Przewoznik, M. ; Brenner, C. ; Riedel, T. ; Flatley, A. ; Polic, B.* ; Busch, D.H.* ; Röcken, M.* ; Mocikat, R.

Critical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma.

Eur. J. Immunol. 45, 2593-2601 (2015)
Verlagsversion DOI
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Little is known on the control of lymphomas by NK cells. Here, we study the role of the NK group 2D (NKG2D) receptor for the immunosurveillance of lymphoma. By using transplantable tumors as well as a λ-myc-transgenic model of endogenously arising lymphoma and NKG2D-deficient mice, we show that NK cells eliminate tumor cells in vivo after receiving two signals. One step involved the activation of NK cells giving rise to IFN-γ expression, which was effected by MHCI(low) tumor cells or DCs. However, this was necessary but not sufficient to mediate cytotoxicity. Triggering cytotoxicity additionally required a second step, which could be mediated by engagement of the NKG2D receptor. Thus, NKG2D-deficient NK cells could become activated in vivo, but they were not able to reject transplanted lymphomas or to degranulate in animals bearing autochthonous lymphomas. Tumor growth in NKG2D-deficient λ-myc-transgenic mice was significantly accelerated compared to NKG2D-competent animals. Whereas the latter developed tumors that lost expression of NKG2D ligands (NKG2D-L) in late disease stages, this did not occur in NKG2D-deficient mice. This indicates that NK cells and the NKG2D receptor play a role for control of lymphomas and that selection for NKG2D-L loss mutants provides a mechanism of tumor escape.
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Endogenous B‐cell Lymphoma ; Nkg2d Ligands ; Nk‐cell Activation ; Tumor Escape ; λ‐myc Mouse
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Quellenangaben Band: 45, Heft: 9, Seiten: 2593-2601 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Begutachtungsstatus Peer reviewed