Abstract
BackgroundAn immunosuppressive microenvironment is critical for cancer initiation and progression. Whether interferon alpha (IFNα) can suppress immune and cancer cells and its involved mechanism still remain largely elusive.MethodsWe examine the expression of interferon alpha/beta receptor-1 (IFNAR1), CD8, CD56 and programmed death ligand 1 (PDL1) in head and neck squamous cell carcinomas (HNSCC). The effect of IFNα on PDL1 and programmed cell death protein 1 (PD1) expression in tumour cells and immune cells was detected in vitro and in vivo.ResultsOverexpression of IFNAR1, MX1 and signal transducer and activator of transcription 1 (Stat1) indicated the endogenous IFNα activation in tumour microenvironment, which correlated with immunosuppression status in HNSCC patients. Moreover, IFNα transcriptionally activated the expression of PDL1 through p-Stat1 (Tyr701) and promoted PD1 expression in immune cells through IFNAR1. The inhibition of IFNα signalling enhanced the cytotoxic activity of nature killer cells. At lastastly, we confirmed the upregulation of PDL1 and PD1 in response to IFNα treatment in both xenograft tumour models and patient-derived xenograft models.ConclusionsOur findings demonstrate that IFNα-induced PDL1 and PD1 expression is a new mechanism of immunosuppression in HNSCC, suggesting that blocking IFNα signalling may enhance the efficacy of immune checkpoint blockade.
Highlights
Head and neck squamous cell carcinoma (HNSCC) accounts for ~90% of head and neck cancer
H Ma et al In this study, we examined the expression of interferon alpha/beta receptor-1 (IFNAR1), CD8, CD56 and programmed death ligand 1 (PDL1) in human head and neck squamous cell carcinomas (HNSCC) tissues, and our results showed that the overexpression of IFNAR1 was significantly associated with the immunosuppressive status in HNSCC
Our results demonstrated that endogenous IFNα can promote the expression of PDL1 in HNSCC cells and programmed cell death 1 (PD1) in immune cells, and that the combination of PD1 and
Summary
Head and neck squamous cell carcinoma (HNSCC) accounts for ~90% of head and neck cancer. Whether interferon alpha (IFNα) can suppress immune and cancer cells and its involved mechanism still remain largely elusive. METHODS: We examine the expression of interferon alpha/beta receptor-1 (IFNAR1), CD8, CD56 and programmed death ligand 1 (PDL1) in head and neck squamous cell carcinomas (HNSCC). The effect of IFNα on PDL1 and programmed cell death protein 1 (PD1) expression in tumour cells and immune cells was detected in vitro and in vivo. RESULTS: Overexpression of IFNAR1, MX1 and signal transducer and activator of transcription 1 (Stat1) indicated the endogenous IFNα activation in tumour microenvironment, which correlated with immunosuppression status in HNSCC patients. CONCLUSIONS: Our findings demonstrate that IFNα-induced PDL1 and PD1 expression is a new mechanism of immunosuppression in HNSCC, suggesting that blocking IFNα signalling may enhance the efficacy of immune checkpoint blockade
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