Yibo Fan1,2, Xiaofang Che1,2, Jinglei Qu1,2, Kezuo Hou1,2, Ti Wen1,2, Zhi Li1,2, Ce Li1,2, Shuo Wang1,2, Ling Xu1,2, Yunpeng Liu3,4, Xiujuan Qu5,6. 1. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. 2. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China. 3. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. cmuliuyunpeng@hotmail.com. 4. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China. cmuliuyunpeng@hotmail.com. 5. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. xiujuanqu@yahoo.com. 6. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China. xiujuanqu@yahoo.com.
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.
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 cancerpatients. 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.
Authors: Eugene Shenderov; Karim Boudadi; Wei Fu; Hao Wang; Rana Sullivan; Alice Jordan; Donna Dowling; Rana Harb; Joseph Schonhoft; Adam Jendrisak; Michael A Carducci; Mario A Eisenberger; James R Eshleman; Jun Luo; Charles G Drake; Drew M Pardoll; Emmanuel S Antonarakis Journal: Prostate Date: 2021-02-26 Impact factor: 4.104
Authors: Dorothee Hölzl; Georg Hutarew; Barbara Zellinger; Hans U Schlicker; Christoph Schwartz; Peter A Winkler; Karl Sotlar; Theo F J Kraus Journal: J Cancer Res Clin Oncol Date: 2021-05-08 Impact factor: 4.553