The PD-L1/PD-1 Axis Blocks Neutrophil Cytotoxicity in Cancer
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Cells - 10(2021), 6 vom: 15. Juni |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yajuk, Olga [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
B7-H1 Antigen |
|---|
| Anmerkungen: |
Date Completed 01.11.2021 Date Revised 01.11.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/cells10061510 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM327506326 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM327506326 | ||
| 003 | DE-627 | ||
| 005 | 20231225200931.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/cells10061510 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1091.xml |
| 035 | |a (DE-627)NLM327506326 | ||
| 035 | |a (NLM)34203915 | ||
| 035 | |a (PII)1510 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yajuk, Olga |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The PD-L1/PD-1 Axis Blocks Neutrophil Cytotoxicity in Cancer |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.11.2021 | ||
| 500 | |a Date Revised 01.11.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a PD-1 | |
| 650 | 4 | |a PD-L1 | |
| 650 | 4 | |a cancer | |
| 650 | 4 | |a metastasis | |
| 650 | 4 | |a neutrophils | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a Cd274 protein, mouse |2 NLM | |
| 650 | 7 | |a Pdcd1 protein, mouse |2 NLM | |
| 650 | 7 | |a Programmed Cell Death 1 Receptor |2 NLM | |
| 700 | 1 | |a Baron, Maya |e verfasserin |4 aut | |
| 700 | 1 | |a Toker, Sapir |e verfasserin |4 aut | |
| 700 | 1 | |a Zelter, Tamir |e verfasserin |4 aut | |
| 700 | 1 | |a Fainsod-Levi, Tanya |e verfasserin |4 aut | |
| 700 | 1 | |a Granot, Zvi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cells |d 2011 |g 10(2021), 6 vom: 15. Juni |w (DE-627)NLM227066421 |x 2073-4409 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2021 |g number:6 |g day:15 |g month:06 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/cells10061510 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2021 |e 6 |b 15 |c 06 | ||