Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood
Open Access
- 8 March 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (11)
- https://doi.org/10.1073/pnas.2016580118
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.This publication has 57 references indexed in Scilit:
- NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRsBlood, 2013
- Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent functionBlood, 2012
- Expansion of a unique CD57+NKG2Chinatural killer cell subset during acute human cytomegalovirus infectionProceedings of the National Academy of Sciences of the United States of America, 2011
- Thy1+ Nk Cells from Vaccinia Virus-Primed Mice Confer Protection against Vaccinia Virus Challenge in the Absence of Adaptive LymphocytesPLoS Pathogens, 2011
- Critical role for the chemokine receptor CXCR6 in NK cell–mediated antigen-specific memory of haptens and virusesNature Immunology, 2010
- Dynamic T cell migration program provides resident memory within intestinal epitheliumThe Journal of Experimental Medicine, 2010
- Cytokine-induced memory-like natural killer cellsProceedings of the National Academy of Sciences of the United States of America, 2009
- Adaptive immune features of natural killer cellsNature, 2009
- Granzyme H destroys the function of critical adenoviral proteins required for viral DNA replication and granzyme B inhibitionThe EMBO Journal, 2007
- T cell– and B cell–independent adaptive immunity mediated by natural killer cellsNature Immunology, 2006