17 Impact of polymorphonuclear cells (PMN) in head and neck cancer progression: A mouse model to investigate time dependent functions of PMN. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Moses, K.; Lang, S.; Brandau, S.
• Is Part Of: Oral oncology. Volume 51:Issue 5(2015:May)
• Page Start: e32
• Publication Date: 2015-05
• Subjects: Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2015.02.019
• Languages: English
• ISSNs: 1368-8375

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title id="st005">Background</title> <p id="sp005">We could previously show that high polymorphonuclear granulocyte (PMN) infiltration in head and neck cancer (HNC) tissues correlated with poor survival of patients with advanced disease. Further in vitro studies showed that human PMN are manipulated by tumor cells to acquire a protumoral phenotype. In order to gain further insight into the mechanisms of PMN-mediated effects during different phases of tumor progression, we characterize PMN expansion, infiltration into tumor tissue and activation by the tumor in a murine in vivo model of HNC.</p> </sec> <sec> <title id="st010">Methods</title> <p id="sp010">Murine HNC cell lines were injected subcutaneous and orthotopic (M. myelohyoideus) into immunocompetent mice. Tissues were analyzed for the presence of different cell types by immunohistochemistry. PMN depletion was performed in mice using Gr1 and Ly6G specific antibodies at different time points of tumor progression. Isolated cells were further analyzed by different assays using flow cytometry.</p> </sec> <sec> <title id="st015">Results</title> <p id="sp015">Tumors were infiltrated by PMN in both sites of tumor growth. Peripheral granulocytes accumulated in spleen and blood upon tumor progression. Depletion of granulocytes in tumor bearing mice resulted in delayed tumor progression. This effect was highly dependent on the time point of PMN depletion, with early time points resulting in the most prominent growth inhibition. Enhanced infiltration by T cells and reduced angiogenesis was observed in PMN depleted animals of different tumor localizations. Furthermore, we could show immunosuppressive functions of tumor induced PMN in vitro, with immature PMN being the most suppressive subset. Additional depletion of CD8 T cells in PMN depleted animals counteracted the delay in tumor progression.</p> </sec> <sec> <title id="st020">Conclusions</title> <p id="sp020">In this model PMN are especially important for the initial steps of tumor formation. Our results suggest that protumoral PMN inhibit an antitumor CD8 T cell response in vivo resulting in accelerated tumor growth. Interference with PMN-mediated tumor progression may offer new treatment options for patients with highly inflammatory tumor growth.</p> </sec> </abstract>