scholarly journals Evaluation of PD-L1 Expression in Tumor Tissue of Patients with Lung Carcinoma and Correlation with Clinical and Demographic Data

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Gustavo Dix Junqueira Pinto ◽  
Luciano de Souza Viana ◽  
Cristovam Scapulatempo Neto ◽  
Sérgio Vicente Serrano

Lung cancer is the leading world cause of cancer-related death, in both genders, and smoking is the main etiological factor. The discovery of immune checkpoints corroborates the hypothesis that ligands presented in tumors modulate the mechanisms of carcinogenesis and the immune activity of tumor microenvironment. Among the most studied coregulatory molecules, PD-1(programmed cell death 1)and its ligand PD-L1(programmed cell death 1 ligand 1)are noteworthy. The present study aims to enhance the understanding of the tumor microenvironment of lung cancer patients who underwent surgery, by means of analysis of PD-L1 expression in tumor cells and in intratumoral immune cells (IICs). It was found that PD-L1 expression was more frequent in tumor cells than in IICs. Collective analysis by Tissue Microarray Assay (TMA) for PD-L1 expression in tumor cells and IICs did not reproduce the findings for separate individual analysis of tumor tissues. Patients with past history of smoking were more likely to express PD-L1 in tumor cells than those who never smoked. Patients with past history of smoking were less likely to have PD-L1 positive IICs compared to those who had never smoked. The immunohistochemical expression of PD-L1 in tumor cells and IICs did not correlate with survival.

2016 ◽  
Vol 11 (2) ◽  
pp. S52 ◽  
Author(s):  
Rachel Krupa ◽  
David Lu ◽  
Ryon Graf ◽  
Jessica Louw ◽  
Lyndsey Dugan ◽  
...  

2018 ◽  
Vol 7 (5) ◽  
pp. R196-R211 ◽  
Author(s):  
Jaafar Jaafar ◽  
Eugenio Fernandez ◽  
Heba Alwan ◽  
Jacques Philippe

Background Monoclonal antibodies blocking the programmed cell death-1 (PD-1) or its ligand (PD-L1) are a group of immune checkpoints inhibitors (ICIs) with proven antitumor efficacy. However, their use is complicated by immune-related adverse events (irAEs), including endocrine adverse events (eAEs). Purpose We review the incidence, time to onset and resolution rate of dysthyroidism induced by PD-1/PD-L1 Ab, and the clinical, biological and radiological findings. We aim to discuss the potential mechanisms of PD-1/PD-L1 Ab-induced dysthyroidism, and to propose a management algorithm. Methods We performed a literature search of available clinical trials regarding PD-1/PD-L1 Ab in the PubMed database. We selected all English language clinical trials that included at least 100 patients. We also present selected case series or reports, retrospective studies and reviews related to this issue. Findings In patients treated with PD-1 Ab, hypothyroidism occurred in 2–10.1% and hyperthyroidism occurred in 0.9–7.8%. When thyroiditis was reported separately, it occurred in 0.34–2.6%. Higher rates were reported when PD-1 Ab were associated with other ICI or chemotherapy. The median time to onset of hyperthyroidism and hypothyroidism after PD-1 Ab initiation was 23–45 days and 2–3.5 months, respectively. Regarding PD-L1 Ab, hypothyroidism occurred in 0–10% and hyperthyroidism in 0.5–2% of treated patients. The average time to onset of dysthyroidism after PD-L1 Ab was variable and ranged from 1 day after treatment initiation to 31 months. Conclusion Dysthyroidism occurs in up to 10% of patients treated with PD-1/PD-L1 Ab. Hypothyroidism and reversible destructive thyroiditis are the most frequent endocrine adverse events (eAE) in PD-1/PD-L1 treated patients. Immune and non-immune mechanisms are potentially involved, independently of the presence of thyroid antibodies.


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