{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:04Z","timestamp":1787028544636,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,18]],"date-time":"2024-08-18T00:00:00Z","timestamp":1723939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre (NCN, Poland)","doi-asserted-by":"publisher","award":["2016\/23\/B\/NZ5\/02622"],"award-info":[{"award-number":["2016\/23\/B\/NZ5\/02622"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre (NCN, Poland)","doi-asserted-by":"publisher","award":["2020\/39\/B\/NZ6\/03513"],"award-info":[{"award-number":["2020\/39\/B\/NZ6\/03513"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"OPUS20","doi-asserted-by":"publisher","award":["2016\/23\/B\/NZ5\/02622"],"award-info":[{"award-number":["2016\/23\/B\/NZ5\/02622"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"OPUS20","doi-asserted-by":"publisher","award":["2020\/39\/B\/NZ6\/03513"],"award-info":[{"award-number":["2020\/39\/B\/NZ6\/03513"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A promising strategy in cancer immunotherapy is to restore or enhance the cytotoxicity of NK cells, among others, by activating the mechanism of antibody-dependent cellular cytotoxicity (ADCC). Monoclonal antibodies targeting tumor antigens, such as rituximab (targeting CD20), induce NK cell-mediated ADCC and have been used to treat B cell malignancies, such as non-Hodgkin lymphoma, but not always successfully. The aim of this study was to analyze the gene expression profile of the NK cells involved in the cytolytic response stimulated by rituximab. NK cells were co-cultured with rituximab-opsonized Raji cells. Sorting into responder and non-responder groups was based on the presence of CD107a, which is a degranulation marker. RNA-seq results showed that the KIT and TNFSF4 genes were strongly down-regulated in the degranulating population of NK cells (responders); this was further confirmed by qRT-PCR. Both genes encode surface proteins with cellular signaling abilities, namely c-KIT and the OX40 ligand. Consistent with our findings, c-KIT was previously reported to correlate inversely with cytokine production by activated NK cells. The significance of these findings for cancer immunotherapy seems essential, as the pharmacological inhibition of c-KIT and OX40L, or gene ablation, could be further tested for the enhancement of the anti-tumor activity of NK cells in response to rituximab.<\/jats:p>","DOI":"10.3390\/ijms25168980","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T07:37:21Z","timestamp":1724053041000},"page":"8980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NK Cell Degranulation Triggered by Rituximab Identifies Potential Markers of Subpopulations with Enhanced Cytotoxicity toward Malignant B Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1545-2547","authenticated-orcid":false,"given":"Marta","family":"Wlodarczyk","sequence":"first","affiliation":[{"name":"Chair and Department of Biochemistry, Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"},{"name":"Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland"},{"name":"Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Torun","sequence":"additional","affiliation":[{"name":"Chair and Department of Biochemistry, Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"},{"name":"Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2628-473X","authenticated-orcid":false,"given":"Abdessamad","family":"Zerrouqi","sequence":"additional","affiliation":[{"name":"Chair and Department of Biochemistry, Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"},{"name":"Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0490-618X","authenticated-orcid":false,"given":"Beata","family":"Pyrzynska","sequence":"additional","affiliation":[{"name":"Chair and Department of Biochemistry, Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"},{"name":"Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(00)03231-1","article-title":"Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: An 11-year follow-up study of a general population","volume":"356","author":"Imai","year":"2000","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1007\/s10875-011-9624-5","article-title":"Primary B-CLL resistance to NK cell cytotoxicity can be overcome in vitro and in vivo by priming NK cells and monoclonal antibody therapy","volume":"32","author":"Veuillen","year":"2012","journal-title":"J. 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