Neutrophils Involvement in Human Thyroid Cancer
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Maria Rosaria Galdiero, MD PhD, Gilda Varricchi, MD PhD, Stefania Loffredo, PhD, Claudio Bellevicine, Tiziana Lansione, Anne Lise Ferrara, Raffaella Iannone, Sarah Di Somma, Francesco Borriello, Eduardo Clery, Maria Triassi, Giancarlo Troncone, Gianni Marone, MD
RATIONALE: Neutrophils are among the tumor-infiltrating immune cells and recent evidences highlight their key roles in the orchestration of the inflammatory responses. Thyroid cancer (TC) is the most frequent cancer of the endocrine system. No studies are so far available investigating the role of neutrophils in TC. The aim of this study was to investigate the role of tumor-associated neutrophils (TANs) in TC.

METHODS: Highly purified human neutrophils (>99%) from healthy donors were stimulated, in vitro, with conditioned media derived from the TC cell lines TPC1 and 8505c (TC-CM). Neutrophil biological properties (e.g. chemotaxis, survival, activation, gene expression and protein release) were investigated.

RESULTS: Soluble factors derived from TC cell lines promoted neutrophil chemotaxis and survival. Neutrophil chemotaxis toward TC-CM was mediated by CXCL8/IL-8. Neutrophil survival induced by TC-CM was mediated by GM-CSF. Moreover, TC-CM induced neutrophil activation (CD11b and CD66b up-regulation, CD62L shedding), morphological changes and modified neutrophil kinetic properties. Furthermore, TC CM induced the release of reactive oxygen species (ROS), the expression of pro-inflammatory factors (CXCL8/IL-8, VEGF-A, TNF-α) and the release of matrix metalloproteinase-9 (MMP-9). In TC patients specimens, tumor-infiltrating neutrophils correlated with larger tumor size (r=0.43, p=0.01, Pearson correlation test).

CONCLUSIONS: TC cell lines produce soluble factors able to ‘educate’ neutrophils towards an activated functional state. Tumor-infiltrating neutrophils in TC patients correlated with tumor size. Further studies are in progress to elucidate the mechanisms underlying the roles of TANs in modifying TC behavior.