OBJECTIVES: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. MATERIALS AND METHODS: We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients. RNA interference was used to downregulate HER2 expression, and PD-L1 protein expression was assessed by flow cytometry using the gastric cancer cell line MKN45. RESULTS: Overexpression of PD-L1 was significantly correlated with tumor invasion (p = 0.011) and associated with poor survival. The number of PD-L1-positive cases increased according to the HER2 score in clinical samples. siRNA-mediated downregulation of HER2 significantly decreased PD-L1 protein expression in MKN45 cells. CONCLUSIONS: PD-L1 expression was associated with poor survival of gastric cancer, and HER2 signaling affects the expression of PD-L1 in gastric cancer. In gastric cancer, PTEN and HER2 are potential candidate biomarkers for developing human antibodies that block PD-L1.
OBJECTIVES: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. MATERIALS AND METHODS: We examined formalin-fixed tumor samples from 144 gastric cancerpatients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients. RNA interference was used to downregulate HER2 expression, and PD-L1 protein expression was assessed by flow cytometry using the gastric cancer cell line MKN45. RESULTS: Overexpression of PD-L1 was significantly correlated with tumor invasion (p = 0.011) and associated with poor survival. The number of PD-L1-positive cases increased according to the HER2 score in clinical samples. siRNA-mediated downregulation of HER2 significantly decreased PD-L1 protein expression in MKN45 cells. CONCLUSIONS:PD-L1 expression was associated with poor survival of gastric cancer, and HER2 signaling affects the expression of PD-L1 in gastric cancer. In gastric cancer, PTEN and HER2 are potential candidate biomarkers for developing human antibodies that block PD-L1.
Authors: Jason I Griffiths; Pierre Wallet; Lance T Pflieger; David Stenehjem; Xuan Liu; Patrick A Cosgrove; Neena A Leggett; Jasmine A McQuerry; Gajendra Shrestha; Maura Rossetti; Gemalene Sunga; Philip J Moos; Frederick R Adler; Jeffrey T Chang; Sunil Sharma; Andrea H Bild Journal: Proc Natl Acad Sci U S A Date: 2020-06-22 Impact factor: 11.205
Authors: Anna Maria Valentini; Federica Di Pinto; Sergio Coletta; Vito Guerra; Raffaele Armentano; Maria Lucia Caruso Journal: Oncol Lett Date: 2019-06-21 Impact factor: 2.967
Authors: Andrea Beer; Hossein Taghizadeh; Ana-Iris Schiefer; Hannah C Puhr; Alexander K Karner; Gerd Jomrich; Sebastian F Schoppmann; Renate Kain; Matthias Preusser; Aysegül Ilhan-Mutlu Journal: Pathol Oncol Res Date: 2020-05-05 Impact factor: 3.201
Authors: Jayati Chakrabarti; Vivien Koh; Nina Steele; Jennifer Hawkins; Yoshiaki Ito; Juanita L Merchant; Jiang Wang; Michael A Helmrath; Syed A Ahmad; Jimmy Bok Yan So; Wei Peng Yong; Yana Zavros Journal: Cancers (Basel) Date: 2021-12-07 Impact factor: 6.575