Positive Programmed Cell Death-Ligand 1 Expression Predicts Poor Treatment Outcomes in Esophageal Squamous Cell Carcinoma Patients Receiving Neoadjuvant Chemoradiotherapy.

BACKGROUND: Programmed cell death-ligand 1 (PD-L1) is present in a subgroup of cancer patients who may be favorable targets for immune checkpoint inhibitor therapies. However, the significance of the PD-L1 expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy remains unclear. METHODS: By means of PD-L1 immunohistochemistry 22C3 pharmDx assay, we evaluate the PD-L1 expression and its association with clinical outcome in 107 ESCC patients receiving neoadjuvant chemoradiotherapy. RESULTS: Patients with positive PD-L1 expression have significantly lower pathological complete response rates (13% versus 32%; P = 0.036) than those with negative PD-L1 expression. Univariate survival analysis found that positive PD-L1 expression were correlated with poor overall survival (P = 0.004) and inferior disease-free survival (P < 0.001). In a multivariate analysis, positive PD-L1 expression was independently associated with the absence of a pathologically complete response (P = 0.044, hazard ratio: 3.542), worse overall survival (P = 0.006, hazard ratio: 2.017), and inferior disease-free survival (P < 0.001, hazard ratio: 2.516). CONCLUSIONS: For patients with ESCC receiving neoadjuvant chemoradiotherapy, positive PD-L1 expression independently predicts the poor chemoradiotherapy response and worse treatment outcome. Thus, our data suggests that PD-L1 may be an influential biomarker for prognostic classification and for immune checkpoint inhibitor therapies in ESCC patients receiving neoadjuvant chemoradiotherapy.

Decrease in regulatory T-cell function in chronic hepatitis C patients receiving pegylated-interferon plus ribavirin.

OBJECTIVES: Regulatory T-cells (Tregs) play an important role in the pathogenesis of chronic hepatitis C (CHC) infection. Pegylated interferon is the standard therapy for CHC patients in Asian countries. This study aimed to evaluate the frequency and function of Tregs in CHC patients receiving combination therapy. METHODS: CHC patients (n=30) who had elevated alanine aminotransferase and underwent combination therapy were included. Clinical data and Treg function were checked at baseline, 12 weeks after treatment, at the end of treatment, and at the end of 24 weeks of follow-up. Treg immunosuppressive activity was measured as the inhibition ratio of conventional T-cell proliferation. RESULTS: Treg-mediated immunosuppression was significantly lower during therapy than at baseline (baseline 44.45%; 12 weeks 18.41% (p=0.042); end of treatment 22.62% (p=0.036); end of follow-up 17.46% (p=0.003)). Treg-mediated immunosuppression was higher in patients with a sustained virological response (SVR) than in those without SVR at the end of follow-up (SVR 24.20%, non-SVR 6.87%; p=0.030). CONCLUSION: Treg-mediated immunosuppression was lower during and after combination therapy, regardless of the treatment response, and higher in patients with SVR than in those without SVR at the end of follow-up.

Guizhi Fuling Wan as a Novel Agent for Intravesical Treatment for Bladder Cancer in a Mouse Model.

Alternative intravesical agents are required to overcome the side effects currently associated with the treatment of bladder cancer. This study used an orthotopic bladder cancer mouse model to evaluate Guizhi Fuling Wan (GFW) as an intravesical agent. The effects of GFW were compared with those of mitomycin-C (Mito-C) and bacille Calmette-Guérin (BCG). We began by evaluating the response of the mouse bladder cancer cell line MB49 to GFW treatment, with regard to cell viability, cell cycle progression and apoptosis. MB49 cells were subsequently implanted into the urothelial walls of the bladder in female C57BL/6 mice. The success of the model was confirmed by the appearance of hematuria and tumor growth in the bladder. Intravesical chemotherapy was administered in accordance with a published protocol. In vitro data revealed that GFW arrested MB49 cell cycle in the G0/G1 phase, resulting in the suppression of cell proliferation and induced apoptosis. One possible mechanism underlying these effects is an increase in intracellular reactive oxygen species (ROS) levels leading to the activation of ataxia telangiectasia-mutated (ATM)/checkpoint kinase 2 (CHK2) and ATM/P53 pathways, thereby mediating cell cycle progression and apoptosis, respectively. This mouse model demonstrates the effectiveness of GFW in the tumor growth, with results comparable to those achieved by using BCG and Mito-C. Furthermore, GFW was shown to cause only mild hematuria. The low toxicity of the compound was confirmed by a complete lack of lesions on bladder tissue, even after 10 consecutive treatments using high concentrations of GFW. These results demonstrate the potential of GFW for the intravesical therapy of bladder cancer.