Details

Autor(en) / Beteiligte

• Fan, Yibo
• Che, Xiaofang
• Qu, Jinglei
• Hou, Kezuo
• Wen, Ti
• Li, Zhi
• Li, Ce
• Wang, Shuo
• Xu, Ling
• Liu, Yunpeng
• Qu, Xiujuan

Titel

Exosomal PD-L1 Retains Immunosuppressive Activity and is Associated with Gastric Cancer Prognosis

Ist Teil von

• Annals of surgical oncology, 2019-10, Vol.26 (11), p.3745-3755

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.