Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion.
10.1038/s41368-022-00197-x
- Author:
Qiuyun FU
1
;
Xingchi LIU
1
;
Houfu XIA
1
;
Yicun LI
2
;
Zili YU
1
;
Bing LIU
1
;
Xuepeng XIONG
3
;
Gang CHEN
4
Author Information
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. Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
3. 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. xiongxuepeng@whu.edu.cn.
4. 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. geraldchan@whu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
B7-H1 Antigen/metabolism*;
CD8-Positive T-Lymphocytes/pathology*;
Carcinoma, Adenoid Cystic/pathology*;
Carcinoma, Squamous Cell/pathology*;
Cell Line, Tumor;
Humans;
Immunosuppression Therapy;
Interferon-gamma/pharmacology*;
Mouth Neoplasms/metabolism*;
Programmed Cell Death 1 Receptor/metabolism*;
Salivary Gland Neoplasms/pathology*
- From:
International Journal of Oral Science
2022;14(1):47-47
- CountryChina
- Language:English
-
Abstract:
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 growth-inhibition 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 (sEVs), 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 sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
