Nasopharyngeal cancer cell‐derived exosomal PD‐L1 inhibits CD8+ T‐cell activity and promotes immune escape

• Published in: Cancer science Vol. 113; no. 9; pp. 3044 - 3054
• Main Authors: Yang, Jie, Chen, Jierong, Liang, Hu, Yu, Yahui
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2022; John Wiley and Sons Inc
• Subjects: Apoptosis; Cancer therapies; CD8 antigen; CD8+ T cells; Cell death; Cell surface; Chemotherapy; Cytotoxicity; Exosomes; Gene expression; IFN‐γ; immune escape; Immune evasion; Interferon; Ligands; Lymphocytes; Lymphocytes T; Nanoparticles; Nasopharyngeal carcinoma; Original; ORIGINAL ARTICLES; Patients; PD-L1 protein; Peripheral blood; Plasma; programmed cell death ligand 1; programmed cell death‐1; Proteins; Radiation therapy; Tumors; Nasopharyngeal carcinoma; CD8+ T cells; IFN-γ; Programmed cell death ligand 1; Programmed cell death-1; Exosomes; Immune escape
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15433

Programmed cell death ligand 1 (PD‐L1) is an immune surface protein that binds to programmed cell death 1 (PD‐1) and allows tumors to evade T‐cell immunity. This study aims to define the role of PD‐L1 shuttled by tumor cell‐derived exosomes in the immune escape of nasopharyngeal carcinoma (NPC). PD‐L1 expression was determined in the exosomes isolated from the plasma of NPC patients or from NPC cells. It was found that PD‐L1 was highly expressed in the exosomes from the plasma of NPC patients and also in the exosomes from NPC cells. PD‐L1/PD‐1 binding was identified in the presence or absence of interferon‐gamma (IFN‐γ) or anti‐PD‐L1 antibody. PD‐L1 expression was elevated following IFN‐γ treatment. Binding of PD‐L1 to PD‐1 was augmented by IFN‐γ and blocked by anti‐PD‐L1 antibody. Following this, CD8+ T cells were sorted out from peripheral blood samples to assess the binding between exosomal PD‐L1 and PD‐1 on the CD8+ T‐cell surface, and to measure the percentage of Ki‐67‐positive T cells. The results indicated that exosomal PD‐L1 bound to the PD‐1 on CD8+ T‐cell surface, leading to a reduced percentage of Ki‐67‐positive CD8+ T cells and downregulated production of cytokines. In vivo data confirmed that exosomal PD‐L1 promoted NPC tumor growth in mice by suppressing CD8+ T‐cell activity. In conclusion, NPC cell‐derived exosomes deliver PD‐L1 to bind to PD‐1 on the CD8+ T‐cell surface, through which cytotoxic CD8+ T‐cell function was attenuated and the immune escape was thus promoted in NPC. Nasopharyngeal carcinoma (NPC) cell‐derived exosomes deliver programmed cell death ligand 1 to bind to programmed cell death 1 on the CD8+ T‐cell surface, through which cytotoxic CD8+ T cell function was attenuated and the immune escape was thus promoted in NPC.