{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:06:23Z","timestamp":1778623583303,"version":"3.51.4"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":955,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015763","name":"Leukaemia UK","doi-asserted-by":"publisher","award":["John Goldman Fellowship"],"award-info":[{"award-number":["John Goldman Fellowship"]}],"id":[{"id":"10.13039\/100015763","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UKRI | Medical Research Council","doi-asserted-by":"publisher","award":["519241101"],"award-info":[{"award-number":["519241101"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["HUNTER"],"award-info":[{"award-number":["HUNTER"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NK cells are promising cellular therapeutics against hematological and solid malignancies. Immunogenetic studies have identified that various activating killer cell Ig-like receptors (KIRs) are associated with cancer outcomes. Specifically, KIR2DS2 has been associated with reduced incidence of relapse following transplant in hematological malignancies and improved outcomes in solid tumors, but the mechanism remains obscure. Therefore, we investigated how KIR2DS2 expression impacts NK cell function. Using a novel flow cytometry panel, we show that human NK cells with high KIR2DS2 expression have enhanced spontaneous activation against malignant B cell lines, liver cancer cell lines, and primary chronic lymphocytic leukemia cells. Surface expression of CD16 was increased on KIR2DS2high NK cells, and, accordingly, KIR2DS2high NK cells had increased activation against lymphoma cells coated with the clinically relevant anti-CD20 Abs rituximab and obinutuzumab. Bulk RNA sequencing revealed that KIR2DS2high NK cells have upregulation of NK-mediated cytotoxicity, translation, and FCGR gene pathways. We developed a novel single-cell RNA-sequencing technique to identify KIR2DS2+ NK cells, and this confirmed that KIR2DS2 is associated with enhanced NK cell\u2013mediated cytotoxicity. This study provides evidence that KIR2DS2 marks a population of NK cells primed for anticancer activity and indicates that KIR2DS2 is an attractive target for NK-based therapeutic strategies.<\/jats:p>","DOI":"10.4049\/jimmunol.2101139","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T16:08:53Z","timestamp":1657814933000},"page":"379-390","source":"Crossref","is-referenced-by-count":14,"title":["KIR2DS2 Expression Identifies NK Cells With Enhanced Anticancer Activity"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1099-3985","authenticated-orcid":false,"given":"Matthew D","family":"Blunt","sequence":"first","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-0598","authenticated-orcid":false,"given":"Andres","family":"Vallejo Pulido","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5090-7503","authenticated-orcid":false,"given":"Jack G","family":"Fisher","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara V","family":"Graham","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3235-5570","authenticated-orcid":false,"given":"Amber D P","family":"Doyle","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Fulton","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J","family":"Carter","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-476X","authenticated-orcid":false,"given":"Marta","family":"Polak","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2306-4974","authenticated-orcid":false,"given":"Peter W M","family":"Johnson","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-089X","authenticated-orcid":false,"given":"Mark S","family":"Cragg","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2211-1831","authenticated-orcid":false,"given":"Francesco","family":"Forconi","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salim I","family":"Khakoo","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, University of Southampton , Southampton,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"2025021008202611200_r1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41577-018-0061-z","article-title":"Natural killer cells and other innate lymphoid cells in cancer. [Published erratum appears in 2018 Nat. Rev. Immunol. 18: 726.]","volume":"18","author":"Chiossone","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"2025021008202611200_r2","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1126\/science.aat2184","article-title":"Natural killers join the fight against cancer","volume":"359","author":"Cerwenka","year":"2018","journal-title":"Science"},{"key":"2025021008202611200_r3","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41590-020-0728-z","article-title":"The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies","volume":"21","author":"Bald","year":"2020","journal-title":"Nat. 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