{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:16:11Z","timestamp":1790817371565,"version":"4.1.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The innate immune lymphocyte lineage natural killer (NK) cell infiltrates tumor environment where it can recognize and eliminate tumor cells. NK cell tumor infiltration is linked to patient prognosis. However, it is unknown if some of these antitumor NK cells leave the tumor environment. In blood-borne cancers, NK cells that have interacted with leukemic cells are recognized by the co-expression of two CD45 isoforms (CD45RARO cells) and\/or the plasma membrane presence of tumor antigens (Ag), which NK cells acquire by trogocytosis. We evaluated solid tumor Ag uptake by trogocytosis on NK cells by performing co-cultures <jats:italic>in vitro<\/jats:italic>. We analyzed NK population subsets by unsupervised dimensional reduction techniques in blood samples from breast tumor (BC) patients and healthy donors (HD). We confirmed that NK cells perform trogocytosis from solid cancer cells <jats:italic>in vitro<\/jats:italic>. The extent of trogocytosis depends on the target cell and the antigen, but not on the amount of Ag expressed by the target cell or the sensitivity to NK cell killing. We identified by FlowSOM (Self-Organizing Maps) several NK cell clusters differentially abundant between BC patients and HD, including anti-tumor NK subsets with phenotype CD45RARO+CD107a+. These analyses showed that <jats:italic>bona-fide<\/jats:italic> NK cells that have degranulated were increased in patients and, additionally, these NK cells exhibit trogocytosis of solid tumor Ag on their surface. However, the frequency of NK cells that have trogocytosed is very low and much lower than that found in hematological cancer patients, suggesting that the number of NK cells that exit the tumor environment is scarce. To our knowledge, this is the first report describing the presence of solid tumor markers on circulating NK subsets from breast tumor patients. This NK cell immune profiling could lead to generate novel strategies to complement established therapies for BC patients or to the use of peripheral blood NK cells in the theranostic of solid cancer patients after treatment.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1199594","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T10:51:54Z","timestamp":1690887114000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["NK cells in peripheral blood carry trogocytosed tumor antigens from solid cancer cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Mauricio","family":"Campos-Mora","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Jacot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Garcin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Lise","family":"Depondt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Constantinides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Alexia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Villalba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-018-9781-4","article-title":"Roles of cytotoxic and helper innate lymphoid cells in cancer","volume":"29","author":"Guillerey","year":"2018","journal-title":"Mamm Genome Off J Int Mamm Genome Soc"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0206-4","article-title":"Human NK cells: surface receptors, inhibitory checkpoints, and translational applications","volume":"16","author":"Sivori","year":"2019","journal-title":"Cell Mol Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"208ra145","DOI":"10.1126\/scitranslmed.3006702","article-title":"Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry","volume":"5","author":"Horowitz","year":"2013","journal-title":"Sci Transl Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13071589","article-title":"Human NK cells in autologous hematopoietic stem cell transplantation for cancer treatment","volume":"13","author":"Orrantia","year":"2021","journal-title":"Cancers"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03026","article-title":"Non-genetically improving the natural cytotoxicity of natural killer (NK) cells","volume":"10","author":"Villalba","year":"2020","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0052-1","article-title":"NK cells for cancer immunotherapy","volume":"19","author":"Shimasaki","year":"2020","journal-title":"Nat Rev Drug Discov"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200205)32:5<1502::AID-IMMU1502>3.0.CO;2-Y","article-title":"Active trans-synaptic capture of membrane fragments by natural killer cells","volume":"32","author":"Tabiasco","year":"2002","journal-title":"Eur J Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051255","article-title":"The role of trogocytosis in the modulation of immune cell functions","volume":"10","author":"Miyake","year":"2021","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061478","article-title":"Lymphocytes and trogocytosis-mediated signaling","volume":"10","author":"Reed","year":"2021","journal-title":"Cells"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2008.32","article-title":"Intercellular trogocytosis plays an important role in modulation of immune responses","volume":"5","author":"Ahmed","year":"2008","journal-title":"Cell Mol Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.791006","article-title":"Gnawing between cells and cells in the immune system: friend or foe? 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