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EnglishDCs are a critical component of immune responses in cancer primarily due to their ability to cross-present tumor-associated antigens. Cross-presentation by DCs in cancer is impaired, which may represent one of the obstacles for the success of cancer immunotherapies. Here, we report that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) blocked crosspresentation by DCs without affecting direct presentation of antigens by these cells. This effect did not require direct cell-cell contact and was associated with transfer of lipids. Neutrophils (PMN) and PMN-MDSC transferred lipid to DCs equally well; however, PMN did not affect DC cross-presentation. PMN-MDSC generate oxidatively truncated lipids previously shown to be involved in impaired cross-presentation by DCs. Accumulation of oxidized lipids in PMN-MDSC was dependent on myeloperoxidase (MPO). MPO-deficient PMN-MDSC did not affect cross-presentation by DCs. Cross-presentation of tumor-associated antigens in vivo by DCs was improved in MDSC-depleted or tumor-bearing MPO-KO mice. Pharmacological inhibition of MPO in combination with checkpoint blockade reduced tumor progression in different tumor models. These data suggest MPO-driven lipid peroxidation in PMN-MDSC as a possible non–cell autonomous mechanism of inhibition of antigen cross-presentation by DCs and propose MPO as potential therapeutic target to enhance the efficacy of current immunotherapies for patients with cancer.
Polymorphonuclear myeloid-derived suppressor cells limit antigen crosspresentation by dendritic cells in cancer / Ugolini, A.; Tyurin, V. A.; Tyurina, Y. Y.; Tcyganov, E. N.; Donthireddy, L.; Kagan, V. E.; Gabrilovich, D. I.; Veglia, F.. - In: JCI INSIGHT. - ISSN 2379-3708. - 5:15(2020). [10.1172/jci.insight.138581]
| Titolo: | Polymorphonuclear myeloid-derived suppressor cells limit antigen crosspresentation by dendritic cells in cancer | |
| Autori: | UGOLINI, Alessio (Primo) | |
| Data di pubblicazione: | 2020 | |
| Rivista: | ||
| Citazione: | Polymorphonuclear myeloid-derived suppressor cells limit antigen crosspresentation by dendritic cells in cancer / Ugolini, A.; Tyurin, V. A.; Tyurina, Y. Y.; Tcyganov, E. N.; Donthireddy, L.; Kagan, V. E.; Gabrilovich, D. I.; Veglia, F.. - In: JCI INSIGHT. - ISSN 2379-3708. - 5:15(2020). [10.1172/jci.insight.138581] | |
| Handle: | http://hdl.handle.net/11573/1456258 | |
| Appartiene alla tipologia: | 01a Articolo in rivista |
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| Ugolini_Polymorphonuclear_2020.pdf | Versione editoriale (versione pubblicata con il layout dell'editore) | Tutti i diritti riservati (All rights reserved) | Open Access Visualizza/Apri |
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