Exosomal PD-L1 Retains Immunosuppressive Activity and is Associated with Gastric Cancer Prognosis.
Ann Surg Oncol
; 26(11): 3745-3755, 2019 Oct.
Article
en En
| MEDLINE
| ID: mdl-31087180
ABSTRACT
BACKGROUND:
A recent study showed that circulating exosomal PD-L1 is an effective predictor for anti-PD-1 therapy in melanomas. Exosomal PD-L1 induced immunosuppression microenvironments in cancer patients. However, its prognostic value and immunosuppressive effect in gastric cancer (GC) were poorly understood.METHODS:
We retrospectively evaluated the prognostic value of exosomal PD-L1 and soluble PD-L1 in preoperative plasma of 69 GC patients. The correlation between exosomal PD-L1 and the T cell counts or cytokine in the plasma was evaluated in 31 metastatic GC patients before chemotherapy.RESULTS:
Overall survival (OS) was significantly lower in the high exosomal PD-L1 group compared with the low exosomal PD-L1 group (P = 0.004). Exosomal PD-L1 was an independent prognostic factor in GC (n = 69, 95% confidence interval = 1.142-7.669, P = 0.026). However, soluble PD-L1 showed no correlation with OS (P = 0.139). Additionally, exosomal PD-L1 in the plasma samples of 31 metastatic GC patients was negatively associated with CD4+ T cell count (P = 0.001, R = - 0.549), CD8+ T-cell count (P = 0.054, R = - 0.349), and granzyme B (P = 0.002, R = - 0.537), indicating that exosomal PD-L1 was associated with immunosuppressive status of GC patients. GC cells also secreted exosomal PD-L1 and were positively associated with the amount of PD-L1 in corresponding GC cell lines. Besides, exosomal PD-L1 significantly decreased T-cell surface CD69 and PD-1 expressions compared with soluble PD-L1 due to its stable and MHC-I expression.CONCLUSIONS:
Overall, exosomal PD-L1 predicts the worse survival and reflects the immune status in GC patients, resulting from a stronger T-cell dysfunction due to its stable and MHC-I expression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Adenocarcinoma
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Terapia de Inmunosupresión
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Exosomas
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Antígeno B7-H1
Tipo de estudio:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ann Surg Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
China