Exosomal PD-L1 Retains Immunosuppressive Activity and is Associated with Gastric Cancer Prognosis
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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.
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.
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.
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.
The National Key Research and Development Program of China (No. 2017YFC1308900). National Natural Science Foundation of China (Nos. 81372546, 81602098, 81673025, 31770963), Science and Technology Plan Project of Liaoning Province (Nos. 2014225013, 2014226033, 2016007010), the general project of Liaoning Province Department of Education (No. LZ2014037), Distinguished professor of Liaoning Province, Project for clinical ability construction of Chinese medicine.
The authors declare no conflicts of interests.
Ethics approval and Consent to Participate
This study was approved by the Human Ethics Review Committee of the First Hospital of China Medical University. All patients agree to participate in our study.
Consent for Publication
The authors certify that no portion of this manuscript has been previously published. Authors listed have approved to submit this manuscript to the journal.
- 13.Stenqvist AC, Nagaeva O, Baranov V, Mincheva-Nilsson L. Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosome-mediated immune privilege of the fetus. J Immunol. 2013; 191(11):5515–23.CrossRefPubMedGoogle Scholar
- 23.Gold B, Cankovic M, Furtado LV, Meier F, Gocke CD. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology. J Mol Diagn. 2015: S1525-1578(15)00047-1.Google Scholar