@article{10.1172/jci.insight.138581, author = {Alessio Ugolini AND Vladimir A. Tyurin AND Yulia Y. Tyurina AND Evgenii N. Tcyganov AND Laxminarasimha Donthireddy AND Valerian E. Kagan AND Dmitry I. Gabrilovich AND Filippo Veglia}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Polymorphonuclear myeloid-derived suppressor cells limit antigen cross-presentation by dendritic cells in cancer}, year = {2020}, month = {8}, volume = {5}, url = {https://insight.jci.org/articles/view/138581}, abstract = {DCs 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 cross-presentation 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.}, number = {15}, doi = {10.1172/jci.insight.138581}, url = {https://doi.org/10.1172/jci.insight.138581}, }