Titel (eng)

Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity

Autor*in

Isaac Dean   University of Birmingham

Menna R. Clatworthy   University of Cambridge / Wellcome Genome Campus

David R. Withers   University of Birmingham

Gianluca Carlesso   AstraZeneca

Matthew R. Hepworth   University of Manchester

Jenny Mjösberg   Karolinska Institutet / Karolinska University Hospital

Simon J. Dovedi   AstraZeneca

Scott A. Hammond   AstraZeneca

Veronika Sexl   University of Veterinary Medicine Vienna

Christian Stockmann   University of Zurich

Syed Murtuza Baker   University of Manchester

Ulrik Lindforss   Karolinska University Hospital

Caroline Nordenvall   Karolinska University Hospital

Rémi Fiancette   University of Birmingham

Veronika Matei-Rascu   University of Birmingham

Bethany C. Kennedy   University of Birmingham

Fabrina Gaspal   University of Birmingham

Claire Willis   University of Birmingham

Christopher A. Tibbitt   Karolinska Institutet

Zhi Li   University of Birmingham

Colin Y. C. Lee   University of Cambridge / Wellcome Genome Campus

Zewen K. Tuong   University of Cambridge / Wellcome Genome Campus

Verlag

Nature Portfolio

Beschreibung (eng)

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.

Sprache des Objekts

Englisch

Datum

2024

Rechte

Dieses Werk bzw. dieser Inhalt steht unter einer
CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Klassifikation

Innate Lymphoid-Cells; Cd8(+) T-Cells; Mouse Nk Cells; Growth-Factor; Adaptive Immunity; Dendritic Cells; In-Vivo; Expression; Programs; Differentiation

Mitglied in der/den Collection(s) (1)