scholarly journals High expression of programmed cell death protein 1 on peripheral blood T‑cell subsets is associated with poor prognosis in metastatic gastric cancer

Author(s):  
Bian Shi ◽  
Qiujian Li ◽  
Xuhui Ma ◽  
Qilong Gao ◽  
Lu Li ◽  
...  
2021 ◽  
Vol 41 (3) ◽  
pp. 259-267
Author(s):  
Min Young Lee ◽  
Chan-Jeoung Park ◽  
Young-Uk Cho ◽  
Eunkyoung You ◽  
Seongsoo Jang ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qian Gao ◽  
Hui-Ting Liu ◽  
Yu-Qin Xu ◽  
Lin Zhang ◽  
Yuan-Ru Liu ◽  
...  

Abstract Background Hypopharyngeal cancer (HPC) is associated with a poor prognosis and a high recurrence rate. Immune escape is one of the reasons for the poor prognosis of malignant tumors. Programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) have been shown to play important roles in immune escape. However, the role of PD-1/PD-L1 in HPC remains unclear. In this experiment, we investigated the effect of exosomes from HPC patient serum on CD8+ T cell function and PD-1/PD-L1 expression and, thus, on prognosis. We hope to provide guidance for the identification of new targets for HPC immunotherapy. Methods PD-1 and CD8 expression in 71 HPC tissues and 16 paracarcinoma tissues was detected by immunohistochemistry. Concurrently, the clinicopathological data of the patients were obtained to conduct correlation analysis. Exosomes were isolated from serum and then identified by Western blotting (WB), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Flow cytometry was used to assess the activity of CD8+ T cells after exosome stimulation. The effects of exosomes on the ability of CD8+ T cells to kill FaDu cells were assessed by CCK-8 assay. The expression of IL-10 and TGF-β1 was measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in HPC tissue samples was evaluated by immunohistochemistry, and the relationship between PD-1/PD-L1 expression and prognosis was investigated with patient specimens. Results PD-1 expression was significantly upregulated on CD8+ T cells in tumor tissues compared with those in normal tissues. The overall survival (OS) and disease-free survival (DFS) of PD-1-overexpressing patients were decreased. Serum exosomes from patients can elevate PD-1 expression on CD8+ T cells and suppress their killing capacity and secretory function. The rate of positive PD-L1 expression was increased in HPC tissues compared with paracancerous tissues. The DFS and OS of the PD-1(+)-PD-L1(+) group were significantly lower than those of the PD-1(−)-PD-L1(−) group. Conclusion Our findings indicate that serum exosomes from HPC patients can inhibit CD8+ T cell function and that the PD-1-PD-L1 pathway plays an important role in the immune escape of HPC. Exosomes combined with immunotherapy may guide the treatment of patients with advanced disease in the future.


Author(s):  
Manman Dai ◽  
Li Zhao ◽  
Ziwei Li ◽  
Xiaobo Li ◽  
Bowen You ◽  
...  

It is well known that chicken CD8+ T cell response is vital to clearing viral infections. However, the differences between T cell subsets expressing CD8 receptors in chicken peripheral blood mononuclear cells (PBMCs) have not been compared. Herein, we used Smart-Seq2 scRNA-seq technology to characterize the difference of chicken CD8high+, CD8high αα+, CD8high αβ+, CD8medium+, and CD4+CD8low+ T cell subsets from PBMCs of avian leukosis virus subgroup J (ALV-J)-infected chickens. Weighted gene co-expression network analysis (WGCNA) and Trend analysis revealed that genes enriched in the “Cytokine–cytokine receptor interaction” pathway were most highly expressed in the CD8high αα+ T cell population, especially T cell activation or response-related genes including CD40LG, IL2RA, IL2RB, IL17A, IL1R1, TNFRSF25, and TNFRSF11, suggesting that CD8high αα+ T cells rather than other CD8 subpopulations were more responsive to ALV-J infections. On the other hand, genes involved in the “FoxO signaling pathway” and “TGF-beta signaling pathway” were most highly expressed in the CD4+CD8low+ (CD8low+) T cell population and the function of CD4+CD8low+ T cells may play roles in negatively regulating the functions of T cells based on the high expression of CCND1, ROCK1, FOXO1, FOXO3, TNFRSF18, and TNFRSF21. The selected gene expressions in CD8+ T cells and CD4+CD8low+ double-positive T cells confirmed by qRT-PCR matched the Smart-Seq2 data, indicating the reliability of the smart-seq results. The high expressions of Granzyme K, Granzyme A, and CCL5 indicated the positive response of CD8+ T cells. Conversely, CD4+CD8+ T cells may have the suppressor activity based on the low expression of activation molecules but high expression of T cell activity suppressor genes. These findings verified the heterogeneity and transcriptional differences of T cells expressing CD8 receptors in chicken PBMCs.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Min Hee Hong ◽  
Su-Jin Shin ◽  
Sung Kwan Shin ◽  
Dae Joon Kim ◽  
Jae Ill Zo ◽  
...  

AbstractWith the increasing oncological potential of immunotherapy, several immune checkpoint modulators are being investigated. The value of immune markers, including programmed cell death ligand-1, programmed cell death-1 (PD-1), inducible co-stimulator (ICOS), lymphocyte activation gene-3, T-cell immunoglobulin, and mucin-dominant containing-3 (TIM-3), is not well known. Using tissue microarrays of 396 patients who underwent surgery for oesophageal squamous cell carcinoma (ESCC), infiltrated T-cell subsets (CD3, CD8, and Foxp3) and checkpoint protein expression were scored. With a median follow-up of 24.8 months, CD3+ TIL subsets (50.0%) had longer median recurrence-free survival (RFS, 55.0 vs 21.4 months) and overall survival (OS, 77.7 vs 35.8 months). Patients with high ICOS expression (46.5%) had longer median RFS (53.9 vs 25.3 months) and OS (88.8 vs 36.9 months). For PD-1, RFS (hazard ratio [HR] 0.67) and OS (HR 0.66) were significantly longer in the high-expression group (45.2%). In the multivariate analysis, high TIM-3 expression (50.8%) had a significant relationship with shorter RFS (HR = 1.52) and OS (HR = 1.60). High CD3+ TIL and T-cell ICOS expression were associated with favourable prognosis, whereas high TIM-3 expression suggested a poor prognosis. Our findings may confer new insights to improve ESCC outcomes beyond the application of PD-1 blockade.


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