Overcoming resistance to immunotherapy by targeting GPR84 in myeloid-derived suppressor cells
作者机构：Biotherapy Center and Cancer CenterThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Department of Medicine-Division of Hematology/OncologyFeinberg School of Medicine Northwestern UniversityChicagoIL60611USA School of Life SciencesZhengzhou UniversityZhengzhouHenan450001China Henan Key Laboratory for Tumor Immunology and BiotherapyZhengzhouHenan450052China State Key Laboratory of Esophageal Cancer Prevention&TreatmentZhengzhou UniversityZhengzhouHenan450052China
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2023年第8卷第5期
页 面：2408-2422页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by grants from the National Natural Science Foundation of China (U1804281,82103427,91942314) the Health Commission of Henan Province (LHGJ20190043,SBGJ202003023)
主 题：esophageal inhibiting suppressor
摘 要：Myeloid-derived suppressor cells(MDSCs)were found to gradually accumulate in the orthotopic esophageal cancer mouse model during tumor *** the roles of MDSCs in promoting tumor growth and inhibiting immune response have been extensively explored,currently,there are still no effective means for targeting MDSCs *** deficiency of specific markers of MDSCs was responsible for the limited strategy to eliminating in *** study identified that GPR84 was exclusively overexpressed on *** was further found that GPR84 was prominently expressed on MDSCs in clinical samples and tumor mouse models,which drives the immunosuppression on CD8^(+)T cells by inhibiting PD-L1 degradation in ***,G-CSF and GM-CSF were found to induce GPR84 expression through the STAT3/C/EBPβsignaling *** addition,GPR84+MDSCs and PD-L1^(+)MDSCs were highly accumulated in anti-PD-1 therapy-resistant patients with esophageal cancer,and high GPR84 signature risk was verified as a negative factor for the overall survival of patients with anti-PD-1 ***,GPR84 antagonism combined with an anti-PD-1 antibody enhanced the antitumor ***,targeting GPR84 enhanced anti-PD-1 efficacy in esophageal cancer and other malignant *** combination therapy has the potential for tumor therapy in clinics.
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