Abstract
Abstract
Recent immunohistological studies have shown that abundant tumour-associated neutrophils (TAN) are present within malignant tumours. TAN can have a significant impact on the tumour microenvironment via release of potent growth factots, chemokines and proteinases that influence tumour progression. The presence of TAN has been associated with poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to identify which factors are responsible for neutrophil recruitment into HNSCC.
The number of TAN within human HNSCC tissue was evaluated by immunohistochemical staining for the neutrophil marker, myeloperoxidase (MPO). The factors secreted by FaDu HNSCC multi-cellular tumour spheroids (MCTS) were analysed by cytokine array and ELISA. Neutrophils isolated from the peripheral blood of healthy volunteers were used to measure neutrophil migration to factors identified from the array. Then the recruitment of neutrophils to MCTS was assessed overtime by flow cytometry in the absence and presence of small molecule inhibitors. FaDu xenograft mouse models were used to confirm the effect of these inhibitors on neutrophil recruitment in-vivo.
MPO staining confirmed the presence of marked numbers of TAN in HNSCC compared to normal oral epithelium. HNSCC MCTS resemble in-vivo tumours, displaying areas of hypoxia, necrosis and cell proliferation. Neutrophils migrated to recombinant CXCL8, CXCL1 and MIF and these chemoattractants were found in the conditioned medium of FaDu MCTS. The recruitment of neutrophils to FaDu MCTS was significantly inhibited when neutrophils were pre-treated with antagonists for CXCR2 and CXCR4, the receptors for CXCL8, CXCL1 and MIF respectively. Moreover, use of the MIF inhibitor, ISO-1caused a dramatic reduction in the number of neutrophils recruited into FaDu MCTS. In-vivo, ISO-1 significantly reduced the number of TAN in xenograft FaDu tumours. Collectively, these data suggest that CXCL8, CXCL1 and MIF in particular are important in the recruitment of TAN into HNSCC.
Citation Format: Hanan A. Niaz. Identification of factors that recruit tumor-associated neutrophils to head and neck squamous cell cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3352. doi:10.1158/1538-7445.AM2015-3352