Article ; Online: The PD-L1/PD-1 Axis Blocks Neutrophil Cytotoxicity in Cancer.
2021 Volume 10, Issue 6
Abstract: 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 ... ...
| Abstract | 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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| MeSH term(s) | Adaptive Immunity ; Animals ; B7-H1 Antigen/metabolism ; B7-H1 Antigen/physiology ; Cell Line, Tumor ; Female ; Humans ; Immune Tolerance ; Immunity, Innate ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Neoplasms/metabolism ; Neoplasms/pathology ; Neutrophils/metabolism ; Neutrophils/physiology ; Programmed Cell Death 1 Receptor/metabolism ; Programmed Cell Death 1 Receptor/physiology |
| Chemical Substances | B7-H1 Antigen ; Cd274 protein, mouse ; Pdcd1 protein, mouse ; Programmed Cell Death 1 Receptor |
| Language | English |
| Publishing date | 2021-06-15 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2661518-6 |
| ISSN | 2073-4409 ; 2073-4409 |
| ISSN (online) | 2073-4409 |
| ISSN | 2073-4409 |
| DOI | 10.3390/cells10061510 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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