phaidra.vetmeduni.ac.at o:3072 DOI 10.1038/s41467-024-44789-z Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived. eng Innate Lymphoid-Cells; Cd8(+) T-Cells; Mouse Nk Cells; Growth-Factor; Adaptive Immunity; Dendritic Cells; In-Vivo; Expression; Programs; Differentiation 2024-06-05T08:00:10.981Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Dean;Isaac; FN:Isaac Dean X-ORCID:https://orcid.org/0000-0002-4750-5335 END:VCARD BEGIN:VCARD VERSION:3.0 N:Clatworthy;Menna R.; FN:Menna R. Clatworthy X-ORCID:https://orcid.org/0000-0002-3340-9828 END:VCARD BEGIN:VCARD VERSION:3.0 N:Withers;David R.; FN:David R. Withers X-ORCID:https://orcid.org/0000-0003-3757-7594 END:VCARD BEGIN:VCARD VERSION:3.0 N:Carlesso;Gianluca; FN:Gianluca Carlesso END:VCARD BEGIN:VCARD VERSION:3.0 N:Hepworth;Matthew R.; FN:Matthew R. Hepworth X-ORCID:https://orcid.org/0000-0002-9613-7858 END:VCARD BEGIN:VCARD VERSION:3.0 N:Mjösberg;Jenny; FN:Jenny Mjösberg X-ORCID:https://orcid.org/0000-0002-1119-0976 END:VCARD BEGIN:VCARD VERSION:3.0 N:Dovedi;Simon J.; FN:Simon J. Dovedi END:VCARD BEGIN:VCARD VERSION:3.0 N:Hammond;Scott A.; FN:Scott A. Hammond X-ORCID:https://orcid.org/0000-0001-5800-4328 END:VCARD BEGIN:VCARD VERSION:3.0 N:Sexl;Veronika; FN:Veronika Sexl X-ORCID:https://orcid.org/0000-0001-9363-0412 END:VCARD BEGIN:VCARD VERSION:3.0 N:Stockmann;Christian; FN:Christian Stockmann END:VCARD BEGIN:VCARD VERSION:3.0 N:Baker;Syed Murtuza; FN:Syed Murtuza Baker X-ORCID:https://orcid.org/0000-0002-6633-333X END:VCARD BEGIN:VCARD VERSION:3.0 N:Lindforss;Ulrik; FN:Ulrik Lindforss END:VCARD BEGIN:VCARD VERSION:3.0 N:Nordenvall;Caroline; FN:Caroline Nordenvall END:VCARD BEGIN:VCARD VERSION:3.0 N:Fiancette;Rémi; FN:Rémi Fiancette X-ORCID:https://orcid.org/0000-0003-1531-9770 END:VCARD BEGIN:VCARD VERSION:3.0 N:Matei-Rascu;Veronika; FN:Veronika Matei-Rascu END:VCARD BEGIN:VCARD VERSION:3.0 N:Kennedy;Bethany C.; FN:Bethany C. Kennedy END:VCARD BEGIN:VCARD VERSION:3.0 N:Gaspal;Fabrina; FN:Fabrina Gaspal END:VCARD BEGIN:VCARD VERSION:3.0 N:Willis;Claire; FN:Claire Willis END:VCARD BEGIN:VCARD VERSION:3.0 N:Tibbitt;Christopher A.; FN:Christopher A. Tibbitt END:VCARD BEGIN:VCARD VERSION:3.0 N:Li;Zhi; FN:Zhi Li X-ORCID:https://orcid.org/0000-0002-0583-1116 END:VCARD BEGIN:VCARD VERSION:3.0 N:Lee;Colin Y. C.; FN:Colin Y. C. Lee X-ORCID:https://orcid.org/0000-0001-8380-4917 END:VCARD BEGIN:VCARD VERSION:3.0 N:Tuong;Zewen K.; FN:Zewen K. Tuong X-ORCID:https://orcid.org/0000-0002-6735-6808 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 1452300 https://phaidra.vetmeduni.ac.at/o:3072 https://phaidra.vetmeduni.ac.at/api/object/o:3072/thumbnail LOMv1.0 discipline