Journal
CELLS
Volume 10, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/cells10061510
Keywords
neutrophils; cancer; metastasis; PD-1; PD-L1
Categories
Funding
- Israel Science Foundation (ISF) [405/18]
- Israel Cancer Research Fund
- Deutsche Forschungsgemeinschaft (DFG)
- Rosetrees Trust
- Samuel and Isabel Friedman Chair in Experimental Medicine
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The PD-L1/PD-1 axis plays a crucial role in mediating immune tolerance and promoting tumor growth by inhibiting anti-tumor immunity. Blocking this axis has been shown to help maintain the anti-tumor functions of the adaptive immune system. Neutrophils consist of distinct subpopulations with either pro- or anti-tumor properties, and PD-L1 expression in neutrophils can either promote or inhibit tumor growth.
The PD-L1/PD-1 axis mediates immune tolerance and promotes tumor growth and progression via the inhibition of anti-tumor immunity. Blocking the interaction between PD-L1 and PD-1 was clinically shown to be beneficial in maintaining the anti-tumor functions of the adaptive immune system. Still, the consequences of blocking the PD-L1/PD-1 axis on innate immune responses remain largely unexplored. In this context, neutrophils were shown to consist of distinct subpopulations, which possess either pro- or anti-tumor properties. PD-L1-expressing neutrophils are considered pro-tumor as they are able to suppress cytotoxic T cells and are propagated with disease progression. That said, we found that PD-L1 expression is not limited to tumor promoting neutrophils, but is also evident in anti-tumor neutrophils. We show that neutrophil cytotoxicity is effectively and efficiently blocked by tumor cell-expressed PD-1. Furthermore, the blocking of either neutrophil PD-L1 or tumor cell PD-1 maintains neutrophil cytotoxicity. Importantly, we show that tumor cell PD-1 blocks neutrophil cytotoxicity and promotes tumor growth via a mechanism independent of adaptive immunity. Taken together, these findings highlight the therapeutic potential of enhancing anti-tumor innate immune responses via blocking of the PD-L1/PD-1 axis.
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