IRF-8 Controls Melanoma Progression by Regulating the Cross Talk between Cancer and Immune Cells within the Tumor Microenvironment

• DOI: 10.1593/neo.121444
• Publication Date: 2015-04-23T13:05:56Z
• Authors: Fabrizio Mattei; Giovanna Schiavoni; Paola Sestili; Francesca Spadaro; Alessandra Fragale; Antonella Sistigu; Valeria Lucarini; Massimo Spada; Massimo Sanchez; Stefania Scala; Angela Battistini; Filippo Belardelli; Lucia Gabriele
• Keywords: Myeloid-derived Suppressor Cell

The transcription factor interferon regulatory factor-8 (IRF-8) is crucial for myeloid cell development and immune response also acts as a tumor suppressor gene. Here, we analyzed the role of IRF-8 in cross talk between melanoma cells tumor-infiltrating leukocytes. B16-F10 transplanted into IRF-8-deficient (IRF-8-/-) mice grow more rapidly, leading to higher numbers lung metastasis, with respect control animals. These events correlated reduced dendritic T infiltration, accumulation myeloid-derived chemokine/chemokine receptor expression profile within microenvironment supporting growth, angiogenesis, metastasis. Noticeably, primary tumors developing IRF-8-/- displayed clear-cut inhibition cells. Injection demethylating agent 5-aza-2′-deoxycytidine melanoma-bearing animals induced intratumoral resulted re-establishment chemokine/ chemokine pattern favoring leukocyte infiltration growth arrest. Importantly, intrinsic was progressively down-modulated during human metastatic tumors. Lastly, directly modulated by soluble factors, among which interleukin-27 (IL-27), released from tumor-bearing mice. Collectively, these results underscore key cells, thus revealing its critical function regulating progression invasiveness.