Editing Natural killer cell (section)

==New findings==

===Innate resistance to HIV===
Recent research suggests specific KIR-MHC class I gene interactions might control innate genetic resistance to certain viral infections, including [[HIV]] and its consequent development of [[AIDS]].<ref name=Lannello2008/> Certain HLA allotypes have been found to determine the progression of HIV to AIDS; an example is the [[HLA-B57]] and [[HLA-B27]] alleles, which have been found to delay progression from HIV to AIDS. This is evident because patients expressing these HLA alleles are observed to have lower viral loads and a more gradual decline in [[T helper cell|CD4<sup>+</sup> T]] cells numbers.  Despite considerable research and data collected measuring the genetic correlation of HLA alleles and KIR allotypes, a firm conclusion has not yet been drawn as to what combination provides decreased HIV and AIDS susceptibility. <!-- Future research will aim to pinpoint relevant KIR/HLA interactions, to develop a vaccine against HIV/AIDS. -->

NK cells can impose immune pressure on HIV, which had previously been described only for T cells and antibodies.<ref name="Alter et al.">{{cite journal | vauthors = Alter G, Heckerman D, Schneidewind A, Fadda L, Kadie CM, Carlson JM, Oniangue-Ndza C, Martin M, Li B, Khakoo SI, Carrington M, Allen TM, Altfeld M | display-authors = 6 | title = HIV-1 adaptation to NK-cell-mediated immune pressure | journal = Nature | volume = 476 | issue = 7358 | pages = 96–100 | date = August 2011 | pmid = 21814282 | pmc = 3194000 | doi = 10.1038/nature10237 }}</ref> HIV mutates to avoid NK cell detection.<ref name="Alter et al."/>

=== Tissue-resident NK cells ===
Most of our current knowledge is derived from investigations of mouse splenic and human peripheral blood NK cells. However, in recent years tissue-resident NK cell populations have been described.<ref name=":0">{{cite journal | vauthors = Yokoyama WM, Sojka DK, Peng H, Tian Z | title = Tissue-resident natural killer cells | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 78 | pages = 149–156 | date = 2013-01-01 | pmid = 24584057 | doi = 10.1101/sqb.2013.78.020354 | doi-access = free }}</ref><ref name=":1">{{cite journal | vauthors = Sojka DK, Plougastel-Douglas B, Yang L, Pak-Wittel MA, Artyomov MN, Ivanova Y, Zhong C, Chase JM, Rothman PB, Yu J, Riley JK, Zhu J, Tian Z, Yokoyama WM | display-authors = 6 | title = Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells | journal = eLife | volume = 3 | pages = e01659 | date = January 2014 | pmid = 24714492 | pmc = 3975579 | doi = 10.7554/elife.01659 | doi-access = free }}</ref> These tissue-resident NK cells share transcriptional similarity to tissue-resident memory T cells described previously. However, tissue-resident NK cells are not necessarily of the memory phenotype, and in fact, the majority of the tissue-resident NK cells are functionally immature.<ref name = Dogra2020>{{cite journal | vauthors = Dogra P, Rancan C, Ma W, Toth M, Senda T, Carpenter DJ, Kubota M, Matsumoto R, Thapa P, Szabo PA, Li Poon MM, Li J, Arakawa-Hoyt J, Shen Y, Fong L, Lanier LL, Farber DL | display-authors = 6 | title = Tissue Determinants of Human NK Cell Development, Function, and Residence | journal = Cell | volume = 180 | issue = 4 | pages = 749–763.e13 | date = February 2020 | pmid = 32059780 | pmc = 7194029 | doi = 10.1016/j.cell.2020.01.022 }}</ref> These specialized NK-cell subsets can play a role in organ homeostasis. For example, NK cells are enriched in the human liver with a specific phenotype and take part in the control of liver fibrosis.<ref name=":2">{{cite journal | vauthors = Hudspeth K, Donadon M, Cimino M, Pontarini E, Tentorio P, Preti M, Hong M, Bertoletti A, Bicciato S, Invernizzi P, Lugli E, Torzilli G, Gershwin ME, Mavilio D | display-authors = 6 | title = Human liver-resident CD56(bright)/CD16(neg) NK cells are retained within hepatic sinusoids via the engagement of CCR5 and CXCR6 pathways | journal = Journal of Autoimmunity | volume = 66 | pages = 40–50 | date = January 2016 | pmid = 26330348 | pmc = 4718768 | doi = 10.1016/j.jaut.2015.08.011 }}</ref><ref name=":3">{{cite journal | vauthors = Fasbender F, Widera A, Hengstler JG, Watzl C | title = Natural Killer Cells and Liver Fibrosis | language = English | journal = Frontiers in Immunology | volume = 7 | pages = 19 | date = 2016 | pmid = 26858722 | pmc = 4731511 | doi = 10.3389/fimmu.2016.00019 | doi-access = free }}</ref> Tissue-resident NK cells have also been identified in sites like bone marrow, spleen and more recently, in lung, intestines and lymph nodes. In these sites, tissue-resident NK cells may act as reservoir for maintaining immature NK cells in humans throughout life.<ref name = Dogra2020 />

=== Adaptive NK cells against leukemia targets ===
Natural killer cells are being investigated as an emerging treatment for patients with acute myeloid leukemia (AML), and cytokine-induced memory-like NK cells have shown promise with their enhanced antileukemia functionality.<ref name="Romee2016"/> It has been shown that this kind of NK cell has enhanced interferon-γ production and cytotoxicity against leukemia cell lines and primary AML blasts in patients.<ref name="Romee2016"/> During a phase 1 clinical trial, five out of nine patients exhibited clinical responses to the treatment, and four patients experienced a complete remission, which suggests that these NK cells have major potential as a successful translational immunotherapy approach for patients with AML in the future.<ref name="Romee2016">{{cite journal | vauthors = Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA, Schappe T, Leong JW, Abdel-Latif S, Schneider SE, Willey S, Neal CC, Yu L, Oh ST, Lee YS, Mulder A, Claas F, Cooper MA, Fehniger TA | display-authors = 6 | title = Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia | journal = Science Translational Medicine | volume = 8 | issue = 357 | pages = 357ra123 | date = September 2016 | pmid = 27655849 | pmc = 5436500 | doi = 10.1126/scitranslmed.aaf2341 }}</ref>