机构:[1]Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.临床科室耳鼻咽喉-头颈外科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[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.
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.
基金:
CAMS initiative for Innovative Medicine of
China (2016-12M-3-019), National Mega projects of China for Major Infectious
Diseases (2017ZX10304402), the 111 Project (B20095).
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
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
JCR分区:
出版当年[2019]版:
Q1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTALQ2ONCOLOGY
最新[2023]版:
Q1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTALQ1ONCOLOGY
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.
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Cao Lin,Li Weisha,Yang Xingjiu,et al.Inhibition of host Ogr1 enhances effector CD8(+) T-cell function by modulating acidic microenvironment[J].CANCER GENE THERAPY.2021,28(10-11):1213-1224.doi:10.1038/s41417-021-00354-0.
APA:
Cao, Lin,Li, Weisha,Yang, Xingjiu,Zhang, Wenlong,Li, Mengyuan...&Gao, Ran.(2021).Inhibition of host Ogr1 enhances effector CD8(+) T-cell function by modulating acidic microenvironment.CANCER GENE THERAPY,28,(10-11)
MLA:
Cao, Lin,et al."Inhibition of host Ogr1 enhances effector CD8(+) T-cell function by modulating acidic microenvironment".CANCER GENE THERAPY 28..10-11(2021):1213-1224