{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:37:11Z","timestamp":1790818631939,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Glycostem Therapeutics BV"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Natural killer (NK) cells are innate lymphocytes capable to recognize and kill virus-infected and cancer cells. In the past years, the use of allogeneic NK cells as anti-cancer therapy gained interest due to their ability to induce graft-versus-cancer responses without causing graft-versus-host disease and multiple protocols have been developed to produce high numbers of activated NK cells. While the ability of these cells to mediate tumor kill has been extensively studied, less is known about their capacity to influence the activity of other immune cells that may contribute to a concerted anti-tumor response in the tumor microenvironment (TME). In this study, we analyzed how an allogeneic off-the-shelf cord blood stem cell-derived NK-cell product influenced the activation of dendritic cells (DC). Crosstalk between NK cells and healthy donor monocyte-derived DC (MoDC) resulted in the release of IFN\u03b3 and TNF, MoDC activation, and the release of the T-cell-recruiting chemokines CXCL9 and CXCL10. Moreover, in the presence of prostaglandin-E2, NK cell\/MoDC crosstalk antagonized the detrimental effect of IL-10 on MoDC maturation leading to higher expression of multiple (co-)stimulatory markers. The NK cells also induced activation of conventional DC2 (cDC2) and CD8+ T cells, and the release of TNF, GM-CSF, and CXCL9\/10 in peripheral blood mononuclear cells of patients with metastatic colorectal cancer. The activated phenotype of MoDC\/cDC2 and the increased release of pro-inflammatory cytokines and T-cell-recruiting chemokines resulting from NK cell\/DC crosstalk should contribute to a more inflamed TME and may thus enhance the efficacy of T-cell-based therapies.<\/jats:p>","DOI":"10.1093\/cei\/uxae007","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T20:23:11Z","timestamp":1707423791000},"page":"159-171","source":"Crossref","is-referenced-by-count":5,"title":["Allogeneic NK cells induce the <i>in vitro<\/i> activation of monocyte-derived and conventional type-2 dendritic cells and trigger an inflammatory response under cancer-associated conditions"],"prefix":"10.1093","volume":"216","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0695-6479","authenticated-orcid":false,"given":"E C","family":"Toffoli","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Amsterdam UMC location Vrije Universiteit , Amsterdam , The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology , Amsterdam , The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A A","family":"van Vliet","sequence":"additional","affiliation":[{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology , Amsterdam , The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases , Amsterdam , The Netherlands"},{"name":"Glycostem Therapeutics , Oss , The Netherlands"},{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Forbes","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam UMC location Vrije Universiteit , Amsterdam , The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology , Amsterdam , The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Arns","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam UMC location Vrije Universiteit , Amsterdam , The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology , Amsterdam , The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H W M","family":"Verheul","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Tuynman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Amsterdam UMC Location Vrije Universiteit , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H J","family":"van der Vliet","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam UMC location Vrije Universiteit , Amsterdam , The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology , Amsterdam , The Netherlands"},{"name":"Lava Therapeutics , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Spanholtz","sequence":"additional","affiliation":[{"name":"Glycostem Therapeutics , Oss , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T D","family":"de Gruijl","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam UMC location Vrije Universiteit , Amsterdam , The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology , Amsterdam , The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"2024042411061825400_CIT0001","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/ni1582","article-title":"Functions of natural killer cells","volume":"9","author":"Vivier","year":"2008","journal-title":"Nat Immunol"},{"key":"2024042411061825400_CIT0002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2014.00159","article-title":"Cross-talks between natural killer cells and distinct subsets of dendritic cells","volume":"5","author":"Ferlazzo","year":"2014","journal-title":"Front Immunol"},{"key":"2024042411061825400_CIT0003","doi-asserted-by":"crossref","first-page":"621254","DOI":"10.3389\/fimmu.2020.621254","article-title":"The natural killer\u2013dendritic cell immune axis in anti-cancer immunity and 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