Polymorphonuclear myeloid-derived suppressor cells and phosphatidylinositol-3 kinase gamma are critical to tobacco-mimicking oral carcinogenesis in mice

• DOI: 10.1136/jitc-2023-007110
• Publication Date: 2023-09-21T16:36:04Z
• Authors: Khoa A Nguyen; Lisa N DePledge; Li Bian; Yao Ke; Von Samedi; Amber A Berning; Philip Owens; Xiao-Jing Wang; Christian D Young
• Keywords: Myeloid-derived Suppressor Cell

Background Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces field of mutations from which tumor arises. Identification ways to prevent the emergence cancer in high-risk patients an ultimate goal for combatting all types cancer, including OSCC. Methods Our study employs mouse model tongue carcinogenesis induced by carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), establish dysplasia and We use conventional histology, immunohistochemistry, multispectral imaging, mass cytometry, novel lines, pharmaceutical inhibition PI3Kγ, T-cell suppression assays transplant models our functional experimentation. Results In study, we identify Ly6G+ granulocytes as abundant immune type mimetic 4NQO. Targeting pharmacologic inhibitor isoform PI3K exclusively expressed myeloid cells, resulted reduced severity, rates Importantly, performed line 4NQO demonstrate these have increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) activity against proliferation PMN-MDSCs play role promoting formation inhibiting regression PI3Kγ-dependent manner. Conclusions Overall, data suggest recruitment sites critical CD8 T thereby permitting malignancy, PI3Kγ inhibitors are one mechanism reduce PMN-MDSC recruitment, immunosuppression tumorigenesis