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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 11; pp. 1 - 12
• Main Authors: Brownlie, Demi, Scharenberg, Marlena, Mold, Jeff E., Hård, Joanna, Kekäläinen, Eliisa, Buggert, Marcus, Nguyen, Son, Wilson, Jennifer N., Al-Ameri, Mamdoh, Ljunggren, Hans-Gustaf, Marquardt, Nicole, Michaëlsson, Jakob
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16-03-2021
• Subjects: Biological Sciences; Blood; Hematology; Lungs; Medicin och hälsovetenskap; Metastases; Natural killer cells; Peripheral blood; Phenotypes; Solid tumors; Tissues; Tumors; lung; adaptive; NK cells; memory; tissue-resident
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2016580118

Human adaptive-like “memory” CD56dimCD16⁺ 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 adaptivelike CD56brightCD16⁻ 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 CD56dimCD16⁺ 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.