Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood

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Brownlie , D , Scharenberg , M , Mold , J E , Hard , J , Kekäläinen , E , Buggert , M , Nguyen , S , Wilson , J N , Al-Ameri , M , Ljunggren , H-G , Marquardt , N & Michaelsson , J 2021 , ' Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 118 , no. 11 , 2016580118 . https://doi.org/10.1073/pnas.2016580118

Title: Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood
Author: Brownlie, Demi; Scharenberg, Marlena; Mold, Jeff E.; Hard, Joanna; Kekäläinen, Eliisa; Buggert, Marcus; Nguyen, Son; Wilson, Jennifer N.; Al-Ameri, Mamdoh; Ljunggren, Hans-Gustaf; Marquardt, Nicole; Michaelsson, Jakob
Contributor: University of Helsinki, Medicum
Date: 2021-03-16
Language: eng
Number of pages: 12
Belongs to series: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
URI: http://hdl.handle.net/10138/329857
Abstract: Human adaptive-like "memory" CD56(dim)CD16(+) natural killer (NK) cells in peripheral blood from cytomegalovirus-seropositive individuals have been extensively investigated in recent years and are currently explored as a treatment strategy for hematological cancers. However, treatment of solid tumors remains limited due to insufficient NK cell tumor infiltration, and it is unknown whether large expansions of adaptive-like NK cells that are equipped for tissue residency and tumor homing exist in peripheral tissues. Here, we show that human lung and blood contains adaptive-like CD56(bright)CD16(-) NK cells with hallmarks of tissue residency, including expression of CD49a. Expansions of adaptive-like lung tissue-resident NK (trNK) cells were found to be present independently of adaptive-like CD56(dim)CD16(+) NK cells and to be hyperresponsive toward target cells. Together, our data demonstrate that phenotypically, functionally, and developmentally distinct subsets of adaptive-like NK cells exist in human lung and blood. Given their tissue-related character and hyperresponsiveness, human lung adaptive-like trNK cells might represent a suitable alternative for therapies targeting solid tumors.
Subject: NK cells
adaptive
memory
lung
tissue-resident
CYTOMEGALOVIRUS-INFECTION
CMV INFECTION
GRANZYME-H
T-CELLS
MEMORY
EXPRESSION
PROMOTES
IMMUNITY
VIRUS
3111 Biomedicine
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