RESUMO
BACKGROUND: APLNR is a G protein-coupled receptor and our previous study had revealed that APLNR could inhibit nasopharyngeal carcinoma (NPC) growth and metastasis. However, the role of APLNR in regulating PD-L1 expression and immune escape in NPC is unknown. METHODS: We analyzed the expression and correlation of APLNR and PD-L1 in NPC tissues and cells. We investigated the effect of APLNR on PD-L1 expression and the underlying mechanism in vitro and in vivo. We also evaluated the therapeutic potential of targeting APLNR in combination with PD-L1 antibody in a nude mouse xenograft model. RESULTS: We found that APLNR was negatively correlated with PD-L1 in NPC tissues and cells. APLNR could inhibit PD-L1 expression by binding to the FERM domain of JAK1 and blocking the interaction between JAK1 and IFNGR1, thus suppressing IFN-γ-mediated activation of the JAK1/STAT1 pathway. APLNR could also inhibit NPC immune escape by enhancing IFN-γ secretion and CD8+ T-cell infiltration and reducing CD8+ T-cell apoptosis and dysfunction. Moreover, the best effect was achieved in inhibiting NPC growth in nude mice when APLNR combined with PD-L1 antibody. CONCLUSIONS: Our study revealed a novel mechanism of APLNR regulating PD-L1 expression and immune escape in NPC and suggested that APLNR maybe a potential therapeutic target for NPC immunotherapy.
Assuntos
Antígeno B7-H1 , Camundongos Nus , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Evasão Tumoral , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Animais , Humanos , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Linhagem Celular Tumoral , Evasão Tumoral/efeitos dos fármacos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação para Baixo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/imunologia , Camundongos Endogâmicos BALB C , Linfócitos T CD8-Positivos/imunologia , Feminino , Fator de Transcrição STAT1/metabolismo , Janus Quinase 1/metabolismo , Masculino , Interferon gama/metabolismo , Receptores de Interferon/genética , Receptores de Interferon/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Solid solutions are garnering substantial attention in the realm of solar energy utilization due to their tunable electronic properties, encompassing band edge positions and charge-carrier mobilities. In this study, we designed and synthesized Co1-xZnxFe2xGa2-2xO4 (0
