| First Author | Ugolini A | Year | 2020 |
| Journal | JCI Insight | Volume | 5 |
| Issue | 15 | PubMed ID | 32584791 |
| Mgi Jnum | J:329645 | Mgi Id | MGI:6753763 |
| Doi | 10.1172/jci.insight.138581 | Citation | Ugolini A, et al. (2020) Polymorphonuclear myeloid-derived suppressor cells limit antigen cross-presentation by dendritic cells in cancer. JCI Insight 5(15) |
| abstractText | 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. |
