Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion  

作　　者：Qiuyun Fu Xingchi Liu Houfu Xia Yicun Li Zili Yu Bing Liu Xuepeng Xiong Gang Chen 

机构地区：[1]The State Key Laboratory Breeding Base of Basic Science of Stomatology&Key Laboratory of Oral Biomedicine Ministry of Education,School and Hospital of Stomatology,Wuhan University,Wuhan,China [2]Department of Oral and Maxillofacial Surgery,School and Hospital of Stomatology,Wuhan University,Wuhan,China [3]Peking University Shenzhen Hospital,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center,Shenzhen,China [4]Frontier Science Center for Immunology and Metabolism,Wuhan University,Wuhan,China

出　　处：《International Journal of Oral Science》2022年第4期541-548,共8页国际口腔科学杂志（英文版）

基　　金：funded by the National Natural Science Foundation of China(81922038);Hubei Natural Science Foundation Out-standing Young Talents Project(2020CFA068);Applied Basic Research Project of Wuhan Municipal Science and Technology Bureau(2020020601012249);The Innovative Research Team of Highlevel Local Universities in Shanghai(SHSMU-ZLCX20212300);Medical Science Advancement Program(Basic Medical Sciences)of Wuhan University(TFJC2018005)。

摘　　要：Interferon-γ(IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma(SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that,compared to oral squamous cell carcinoma cells(a type of immunologically hot cancer), SACC cells were less sensitive to the growthinhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment.In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1(PD-L1) on SACC cell-derived small extracellular vesicles(s EVs), which subsequently induced the apoptosis of CD8+T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating s EVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via s EV PD-L1,which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.

关 键 词：SALIVARY INVASION programmed 

分 类 号：R739.87[医药卫生—肿瘤]