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

By Nicole Marquardt, Marlena Scharenberg, Jeffrey E. Mold, Joanna Hård, Eliisa Kekäläinen, Marcus Buggert, Son Nguyen, Jennifer N Wilson, Mamdoh Al-Ameri, Hans-Gustaf Ljunggren, Jakob Michaëlsson

Posted 20 Dec 2019
bioRxiv DOI: 10.1101/2019.12.20.883785

Human adaptive-like "memory" CD56dimCD16+ 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 CD56brightCD16- NK cells with hallmarks of tissue-residency, including expression of CD49a. Expansions of adaptive-like lung tissue-resident (tr)NK cells were found to be present independently of adaptive-like CD56dimCD16+ NK cells and to be hyperresponsive towards 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. ### Competing Interest Statement The authors have declared no competing interest.

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