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
,
2
;
Xingchi LIU
1
,
2
;
Houfu XIA
1
,
2
;
Yicun LI
3
;
Zili YU
1
,
2
;
Bing LIU
1
,
2
;
Xuepeng XIONG
1
,
4
;
Gang CHEN
1
,
5
Author Information
1. The State Key Laboratory Breeding Base of Basic Science of Stomatology &
2. Key Laboratory of Oral Biomedicine Ministry of Education, 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. Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. xiongxuepeng@whu.edu.cn.
5. 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.
