Journal
CANCER SCIENCE
Volume 113, Issue 9, Pages 3044-3054Publisher
WILEY
DOI: 10.1111/cas.15433
Keywords
CD8+T cells; exosomes; IFN-gamma; immune escape; nasopharyngeal carcinoma; programmed cell death ligand 1; programmed cell death-1
Categories
Funding
- China Postdoctoral Science Foundation [2019M663293]
- National Natural Science Foundation of China [81902750, 82002855]
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This study found that PD-L1 is highly expressed in exosomes from the plasma of NPC patients and NPC cells. Exosomal PD-L1 binds to PD-1 on CD8+ T-cell surface, attenuates the cytotoxic function of CD8+ T cells, and promotes immune evasion in NPC.
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-gamma) or anti-PD-L1 antibody. PD-L1 expression was elevated following IFN-gamma treatment. Binding of PD-L1 to PD-1 was augmented by IFN-gamma 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.
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