Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-09-01
|
| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-022-00197-x |
| _version_ | 1828203616192692224 |
|---|---|
| author | Qiuyun Fu Xingchi Liu Houfu Xia Yicun Li Zili Yu Bing Liu Xuepeng Xiong Gang Chen |
| author_facet | Qiuyun Fu Xingchi Liu Houfu Xia Yicun Li Zili Yu Bing Liu Xuepeng Xiong Gang Chen |
| author_sort | Qiuyun Fu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:09:00Z |
| format | Article |
| id | doaj.art-5f2bfcfb04ab41d29c6d8ed3443bcf6c |
| institution | Directory Open Access Journal |
| issn | 1674-2818 2049-3169 |
| language | English |
| last_indexed | 2024-04-12T12:09:00Z |
| publishDate | 2022-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj.art-5f2bfcfb04ab41d29c6d8ed3443bcf6c2022-12-22T03:33:38ZengNature Publishing GroupInternational Journal of Oral Science1674-28182049-31692022-09-011411810.1038/s41368-022-00197-xInterferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretionQiuyun Fu0Xingchi Liu1Houfu Xia2Yicun Li3Zili Yu4Bing Liu5Xuepeng Xiong6Gang Chen7The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan UniversityPeking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterThe State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan UniversityAbstract 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.https://doi.org/10.1038/s41368-022-00197-x |
| spellingShingle | Qiuyun Fu Xingchi Liu Houfu Xia Yicun Li Zili Yu Bing Liu Xuepeng Xiong Gang Chen Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion International Journal of Oral Science |
| title | Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion |
| title_full | Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion |
| title_fullStr | Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion |
| title_full_unstemmed | Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion |
| title_short | Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion |
| title_sort | interferon γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion |
| url | https://doi.org/10.1038/s41368-022-00197-x |
| work_keys_str_mv | AT qiuyunfu interferonginducesimmunosuppressioninsalivaryadenoidcysticcarcinomabyregulatingprogrammeddeathligand1secretion AT xingchiliu interferonginducesimmunosuppressioninsalivaryadenoidcysticcarcinomabyregulatingprogrammeddeathligand1secretion AT houfuxia interferonginducesimmunosuppressioninsalivaryadenoidcysticcarcinomabyregulatingprogrammeddeathligand1secretion AT yicunli interferonginducesimmunosuppressioninsalivaryadenoidcysticcarcinomabyregulatingprogrammeddeathligand1secretion AT ziliyu interferonginducesimmunosuppressioninsalivaryadenoidcysticcarcinomabyregulatingprogrammeddeathligand1secretion AT bingliu interferonginducesimmunosuppressioninsalivaryadenoidcysticcarcinomabyregulatingprogrammeddeathligand1secretion AT xuepengxiong interferonginducesimmunosuppressioninsalivaryadenoidcysticcarcinomabyregulatingprogrammeddeathligand1secretion AT gangchen interferonginducesimmunosuppressioninsalivaryadenoidcysticcarcinomabyregulatingprogrammeddeathligand1secretion |