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

Yibo Fan MD, PhD, Xiaofang Che MD, PhD, Jinglei Qu MD, Kezuo Hou MD, Ti Wen MD, PhD, Zhi Li MD, PhD, Ce Li PhD, Shuo Wang MD, Ling Xu MD, PhD, Yunpeng Liu MD, PhD, Xiujuan Qu MD, PhD
Translational Research and Biomarkers
Volume 26, Issue 11 / October , 2019

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.

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