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Inhibition of host Ogr1 enhances effector CD8(+) T-cell function by modulating acidic microenvironment

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机构: [1]Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. [2]NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China. [3]National Cancer Center/Cancer Hospital, CAMS & PUMC, Beijing, China.
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Immunotherapies for cancer, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to a long-lasting clinical response. But the therapeutic response rate remains low on account of many tumors that have evolved sophisticated strategies to evade immune surveillance. Solid tumors are characterized by the highly acidic microenvironment, which may weaken the effectiveness of antitumor immunity. Here, we explored a promising therapeutic development deployed by pH manipulation for avoiding immunoevasion. The highly acidified microenvironment of melanoma induces the expression of G-protein-coupled receptor (Ogr1) in T cells, which weakened their effective function and promote tumor growth. Ogr1 inhibition reactivate CD8(+) T cells and have a cytotoxic role by reducing the activity of high glycolysis, resulting in comparatively low acidification of the tumor microenvironment, and leads to tumor suppression. In addition, the adoptive transfer of Ogr1(-/-)-CD8(+) T cells enhanced the antitumor responses, with the potential for immediate clinical transformation.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 生物工程与应用微生物 2 区 遗传学 3 区 医学:研究与实验 3 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 生物工程与应用微生物 3 区 遗传学 3 区 医学:研究与实验 4 区 肿瘤学
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出版当年[2019]版:
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q2 ONCOLOGY
最新[2023]版:
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. [2]NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China.
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