000132942 001__ 132942
000132942 005__ 20240229105040.0
000132942 0247_ $$2doi$$a10.1158/2326-6066.CIR-17-0550
000132942 0247_ $$2pmid$$apmid:29514797
000132942 0247_ $$2ISSN$$a2326-6066
000132942 0247_ $$2ISSN$$a2326-6074
000132942 0247_ $$2altmetric$$aaltmetric:34134024
000132942 037__ $$aDKFZ-2018-00581
000132942 041__ $$aeng
000132942 082__ $$a610
000132942 1001_ $$0P:(DE-He78)0f643e43f006f9ce6666909ec4f79a2f$$aPahl, Jens$$b0$$eFirst author$$udkfz
000132942 245__ $$aCD16A Activation of NK Cells Promotes NK Cell Proliferation and Memory-Like Cytotoxicity against Cancer Cells.
000132942 260__ $$aPhiladelphia, Pa.$$bAACR$$c2018
000132942 3367_ $$2DRIVER$$aarticle
000132942 3367_ $$2DataCite$$aOutput Types/Journal article
000132942 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1527241143_21565
000132942 3367_ $$2BibTeX$$aARTICLE
000132942 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000132942 3367_ $$00$$2EndNote$$aJournal Article
000132942 520__ $$aCD16A is a potent cytotoxicity receptor on human natural killer (NK) cells, which can be exploited by therapeutic bispecific antibodies. So far, the effects of CD16A-mediated activation on NK cell effector functions beyond classical antibody-dependent cytotoxicity have remained poorly elucidated. Here, we investigated NK cell responses after exposure to therapeutic antibodies such as the tetravalent bispecific antibody AFM13 (CD30/CD16A), designed for the treatment of Hodgkin lymphoma and other CD30+ lymphomas. Our results reveal that CD16A engagement enhanced subsequent IL2- and IL15-driven NK cell proliferation and expansion. This effect involved the upregulation of CD25 (IL2Rα) and CD132 (γc) on NK cells, resulting in increased sensitivity to low-dose IL2 or to IL15. CD16A engagement initially induced NK cell cytotoxicity. The lower NK cell reactivity observed 1 day after CD16A engagement could be recovered by reculture in IL2 or IL15. After reculture in IL2 or IL15, these CD16A-experienced NK cells exerted more vigorous IFNγ production upon restimulation with tumor cells or cytokines. Importantly, after reculture, CD16A-experienced NK cells also exerted increased cytotoxicity toward different tumor targets, mainly through the activating NK cell receptor NKG2D. Our findings uncover a role for CD16A engagement in priming NK cell responses to restimulation by cytokines and tumor cells, indicative of a memory-like functionality. Our study suggests that combination of AFM13 with IL2 or IL15 may boost NK cell antitumor activity in patients by expanding tumor-reactive NK cells and enhancing NK cell reactivity, even upon repeated tumor encounters. Cancer Immunol Res; 6(5); 517-27. ©2018 AACR.
000132942 536__ $$0G:(DE-HGF)POF3-314$$a314 - Tumor immunology (POF3-314)$$cPOF3-314$$fPOF III$$x0
000132942 588__ $$aDataset connected to CrossRef, PubMed,
000132942 7001_ $$aKoch, Joachim$$b1
000132942 7001_ $$0P:(DE-He78)63c7f59c86b4d0aea6cb35656305e1a4$$aGötz, Jana$$b2$$udkfz
000132942 7001_ $$0P:(DE-He78)7c776439971ef21f36ac730cfbff7fff$$aArnold, Annette$$b3$$udkfz
000132942 7001_ $$aReusch, Uwe$$b4
000132942 7001_ $$aGantke, Thorsten$$b5
000132942 7001_ $$aRajkovic, Erich$$b6
000132942 7001_ $$aTreder, Martin$$b7
000132942 7001_ $$0P:(DE-He78)d2b4dd8bdffe4aaa0f5e30e91587766f$$aCerwenka, Adelheid$$b8$$eLast author$$udkfz
000132942 773__ $$0PERI:(DE-600)2732517-9$$a10.1158/2326-6066.CIR-17-0550$$gVol. 6, no. 5, p. 517 - 527$$n5$$p517 - 527$$tCancer immunology research$$v6$$x2326-6074$$y2018
000132942 909CO $$ooai:inrepo02.dkfz.de:132942$$pVDB
000132942 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0f643e43f006f9ce6666909ec4f79a2f$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000132942 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)63c7f59c86b4d0aea6cb35656305e1a4$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000132942 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7c776439971ef21f36ac730cfbff7fff$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000132942 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)d2b4dd8bdffe4aaa0f5e30e91587766f$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000132942 9131_ $$0G:(DE-HGF)POF3-314$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTumor immunology$$x0
000132942 9141_ $$y2018
000132942 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000132942 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000132942 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000132942 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCANCER IMMUNOL RES : 2015
000132942 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000132942 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000132942 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000132942 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000132942 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCANCER IMMUNOL RES : 2015
000132942 9201_ $$0I:(DE-He78)D080-20160331$$kD080$$lNachwuchsgruppe Angeborene Immunität$$x0
000132942 980__ $$ajournal
000132942 980__ $$aVDB
000132942 980__ $$aI:(DE-He78)D080-20160331
000132942 980__ $$aUNRESTRICTED