期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 69, 期 8, 页码 1505-1517出版社
SPRINGER
DOI: 10.1007/s00262-020-02558-z
关键词
Cancer immunotherapy; Immune checkpoint inhibitor; Inhibitory receptor; Resistance; Innate immunity
资金
- Swiss National Science Foundation [320030_162575]
- University of Basel
- Swiss National Science Foundation (SNF) [320030_162575] Funding Source: Swiss National Science Foundation (SNF)
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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