Wen-Cheng Chen1,2, Chia-Hsuan Lai1, Huei-Chieh Chuang3, Paul-Yang Lin3, Miao-Fen Chen1,2. 1. Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan. 2. Chang Gung University, College of Medicine, Taiwan. 3. Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Taiwan.
Abstract
BACKGROUND: The purpose of this study was to present our assessment of the significance of myeloid-derived suppressor cells (MDSCs) in head and neck squamous cell carcinoma (HNSCC). METHODS: We examined the percentage of MDSCs in the peripheral blood of patients with HNSCC. The relationship among MDSC recruitment, tumor progression, and cyclooxygenase (COX)-2 inhibition was also evaluated by animal models. RESULTS: Circulating MDSCs were significantly increased in patients with HNSCC compared with healthy people, and this was associated with the clinical tumor burden. In immunocompetent 4-nitroquinoline-1-oxide (4-NQO)-induced oral tumor and immunocompromised tumor implantation animal models, MDSC recruitment was associated with the duration of 4-NQO treatment and tumor progression. The responsible mechanisms included the suppressive ability of T-cell proliferation and augmenting angiogenesis by MDSC. Blockade of COX-2 attenuated the induction and function of MDSCs and subsequently inhibited tumor growth. CONCLUSION: The levels of MDSC are linked with tumor progression in HNSCC. Moreover, targeting COX-2 could be a promising strategy for the treatment of HNSCC.
BACKGROUND: The purpose of this study was to present our assessment of the significance of myeloid-derived suppressor cells (MDSCs) in head and neck squamous cell carcinoma (HNSCC). METHODS: We examined the percentage of MDSCs in the peripheral blood of patients with HNSCC. The relationship among MDSC recruitment, tumor progression, and cyclooxygenase (COX)-2 inhibition was also evaluated by animal models. RESULTS: Circulating MDSCs were significantly increased in patients with HNSCC compared with healthy people, and this was associated with the clinical tumor burden. In immunocompetent 4-nitroquinoline-1-oxide (4-NQO)-induced oral tumor and immunocompromised tumor implantation animal models, MDSC recruitment was associated with the duration of 4-NQO treatment and tumor progression. The responsible mechanisms included the suppressive ability of T-cell proliferation and augmenting angiogenesis by MDSC. Blockade of COX-2 attenuated the induction and function of MDSCs and subsequently inhibited tumor growth. CONCLUSION: The levels of MDSC are linked with tumor progression in HNSCC. Moreover, targeting COX-2 could be a promising strategy for the treatment of HNSCC.
Authors: Sarah Greene; Yvette Robbins; Wojciech K Mydlarz; Angel P Huynh; Nicole C Schmitt; Jay Friedman; Lucas A Horn; Claudia Palena; Jeffrey Schlom; Dean Y Maeda; John A Zebala; Paul E Clavijo; Clint Allen Journal: Clin Cancer Res Date: 2019-12-17 Impact factor: 12.531