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- Title
PD-1+ natural killer cells in human non-small cell lung cancer can be activated by PD-1/PD-L1 blockade.
- Authors
Trefny, Marcel P.; Kaiser, Monika; Stanczak, Michal A.; Herzig, Petra; Savic, Spasenija; Wiese, Mark; Lardinois, Didier; Läubli, Heinz; Uhlenbrock, Franziska; Zippelius, Alfred
- 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.
- Subjects
KILLER cells; NON-small-cell lung carcinoma; CELL receptors; PROGRAMMED cell death 1 receptors; IMMUNE checkpoint inhibitors
- Publication
Cancer Immunology, Immunotherapy, 2020, Vol 69, Issue 8, p1505
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-020-02558-z