Expression of Immune Checkpoint Regulators, Cytotoxic T-Lymphocyte Antigen-4, and Programmed Death-Ligand 1 in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx with a poor prognosis. Targeting immune checkpoint is one of the new promising lines in cancer treatment. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) are immune checkpoints that regulate T-cell immune function. AIM: This work aimed to assess the immunohistochemical expression of PD-L1 and CTLA-4 in NPC and their ability to predict survival and response therapy and to check their validity as immunotherapy targets. Twenty-six cases of NPC were studied by immunohistochemistry for PD-L1 and CTLA-4 and by nested polymerase chain reaction followed by DNA sequencing for the presence of EBNA-1 gene of Epstein-Barr virus (EBV). All investigated cases were diagnosed and treated in the Zagazig University Hospital in the period from August 2015 to July 2018. EBNA-1 gene was identified in 84.6% of the cases. Whereas the expression of PD-L1 was noted in 46.2% of all cases studied, 54.6% of EBV-associated NPCs were found to express PD-L1. There was a significant association between PD-L1 expression and the advanced stage of the tumor (P<0.001). CTLA-4 expression was observed in 88.4% of all NPC cases as cytoplasmic staining in both tumor cells and tumor-infiltrating lymphocytes. CTLA-4 expression in lymphocytes was associated with the presence of EBV. A significant association was detected between CTLA-4 and tumor-infiltrating lymphocyte expression on one side and the stage of the tumor on the other. High expression of CTLA-4 was significantly associated with disease progression and worse overall survival. CONCLUSION: PD-L1 and CTLA-4 are adverse prognostic markers in NPC. The authors propose that targeted therapy against PD-L1 and CTLA-4 will be a hopeful therapy for cases of NPC with resistance to concurrent chemoradiation treatment in Egypt, especially EBV-associated cases.

Association between Glutamine 27 Polymorphism of B2 Adrenergic Receptor and Bronchial Asthma in Children.

Bronchial asthma is one of the most prevailed non-communicable diseases among Egyptian children. Genetic-environmental interaction can influence the nature of asthma and ß2 agonists are the most commonly prescribed bronchodilators for relieving asthma symptoms. This study was conducted to investigate the possible relationship between Gln27/Glu polymorphism of ADRß2 and bronchial asthma susceptibility, severity and responsiveness to Albuterol in Egyptian children. A case control study of one hundred Egyptian children, where all contributors were genotyped using allele-specific Polymerase chain reaction (AS-PCR). Cases were selected and classified according to GINA guidelines and spirometerically assessed to evaluate pulmonary functions. There were no statistically significant variances between patients and control regarding Gln27/Glu polymorphism. Gln27 genotype has positive association with both asthma severity and drug response. In conclusion; B2 adrenergic receptor polymorphism at codon 27 is not associated with asthma susceptibility; however, it can be a determinant factor for asthma severity and bronchodilating response to B2 agonists in Egyptian asthmatic children.