1.Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion.
Qiuyun FU ; Xingchi LIU ; Houfu XIA ; Yicun LI ; Zili YU ; Bing LIU ; Xuepeng XIONG ; Gang CHEN
International Journal of Oral Science 2022;14(1):47-47
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.
B7-H1 Antigen/metabolism*
;
CD8-Positive T-Lymphocytes/pathology*
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Carcinoma, Adenoid Cystic/pathology*
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Carcinoma, Squamous Cell/pathology*
;
Cell Line, Tumor
;
Humans
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Immunosuppression Therapy
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Interferon-gamma/pharmacology*
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Mouth Neoplasms/metabolism*
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Programmed Cell Death 1 Receptor/metabolism*
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Salivary Gland Neoplasms/pathology*