Erschienen in:
15.04.2020 | Original Article
PD-1+ natural killer cells in human non-small cell lung cancer can be activated by PD-1/PD-L1 blockade
verfasst von:
Marcel P. Trefny, Monika Kaiser, Michal A. Stanczak, Petra Herzig, Spasenija Savic, Mark Wiese, Didier Lardinois, Heinz Läubli, Franziska Uhlenbrock, Alfred Zippelius
Erschienen in:
Cancer Immunology, Immunotherapy
|
Ausgabe 8/2020
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Abstract
Natural killer (NK) cells are critically involved in anti-tumor immunity by targeting tumor cells. In this study, we show that intratumoral NK cells from NSCLC patients expressed elevated levels of the immune checkpoint receptor PD-1 on their cell surface. In contrast to the expression of activating receptors, PD-1+ NK cells co-expressed more inhibitory receptors compared to PD-1− NK cells. Intratumoral NK cells were less functional compared to peripheral NK cells, and this dysfunction correlated with PD-1 expression. Tumor cells expressing PD-L1 inhibited the functionality of PD-1+ NK cells in ex vivo models and induced PD-1 clustering at the immunological synapse between NK cells and tumor cells. Notably, treatment with PD-1 blockade was able to reverse PD-L1-mediated inhibition of PD-1+ NK cells. Our findings highlight the therapeutic potential of PD-1+ NK cells in immune checkpoint blockade and could guide the development of NK cell-stimulating agents in combination with PD-1 blockade.