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01-08-2020 | NSCLC | Original Article

PD-1⁺ natural killer cells in human non-small cell lung cancer can be activated by PD-1/PD-L1 blockade

Authors: Marcel P. Trefny, Monika Kaiser, Michal A. Stanczak, Petra Herzig, Spasenija Savic, Mark Wiese, Didier Lardinois, Heinz Läubli, Franziska Uhlenbrock, Alfred Zippelius

Published in: Cancer Immunology, Immunotherapy | Issue 8/2020

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.

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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: Marcel P. Trefny
Monika Kaiser
Michal A. Stanczak
Petra Herzig
Spasenija Savic
Mark Wiese
Didier Lardinois
Heinz Läubli
Franziska Uhlenbrock
Alfred Zippelius
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Cancer Immunotherapy
Published in: Cancer Immunology, Immunotherapy / Issue 8/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02558-z

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