High-dimensional analysis reveals a distinct population of adaptive-like tissue-resident NK cells in human lung

Marquardt, N.; Scharenberg, M.; Mold, J. E.; Hard, J.; Kekalainen, E.; Buggert, M.; Nguyen, S.; Wilson, J. N.; Al-Ameri, M.; Ljunggren, H.-G.; Michaelsson, J.

doi:10.1101/2019.12.20.883785

bioRxiv · 10.1101/2019.12.20.883785

High-dimensional analysis reveals a distinct population of adaptive-like tissue-resident NK cells in human lung

Marquardt, N.·Scharenberg, M.·Mold, J. E.·Hard, J.·Kekalainen, E.·Buggert, M.·Nguyen, S.·Wilson, J. N.·Al-Ameri, M.·Ljunggren, H.-G.·Michaelsson, J.

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Abstract

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 StatementThe authors have declared no competing interest.Abbreviations:EomesEomesoderminFITCFluorescein isothiocyanateHCMVHuman cytomegalovirusILCInnate lymphoid cellKIRKiller cell immunoglobulin-like receptorNKNatural killerPEPhycoerythrinROSReactive oxygen speciesView Full Text

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Marquardt, N., Scharenberg, M., Mold, J. E., Hard, J., Kekalainen, E., Buggert, M., Nguyen, S., Wilson, J. N., Al-Ameri, M., Ljunggren, H.-G., Michaelsson, J.. 2019-12-20. High-dimensional analysis reveals a distinct population of adaptive-like tissue-resident NK cells in human lung. https://doi.org/10.1101/2019.12.20.883785

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