Abstract Background: The pro-angiogenic IL-8 pathway has already been associated with resistance to VEGF-targeted therapies in various tumour types, particularly in melanoma. IL-8 expression is higher in tumour as compared to normal tissues and both tumour and endothelial cells express this chemokine and its receptors, CXCR1 and CXCR2. Uveal melanoma (UM) is a highly vascularised tumour that is generally treated with radiations (RT). In a previous pre-clinical study (Sudaka A. et al., Invest. New Drugs, 2012, Jun 20), we reported that RT-associated anti-angiogenic therapy has more than additive effects by modulating VEGF levels and allowing to deliver lower radiation doses for identical cytotoxic effects. Aim: In order to better understand the microenvironment contribution to treatment efficacy in UM we investigated the release of IL-8 in response to the anti-angiogenic drug Bevacizumab, and the cross-talk between IL-8 and VEGF signalling. Materials and methods: OCM-1 uveal melanoma cell line and Huvec cells were grown in transwell plates. Bevacizumab was used at a final concentration of 2.5 mg/ml and cells were irradiated with a 6Gy dose. Il-8 concentrations were determined by ELISA assay. Results: Bevacizumab alone or combined with RT induced a 6 fold decrease in IL-8 concentration in culture medium from OCM-1 cells grown alone (Bev vs control/CT p<0,001%; Bev vs CT p<0,01%), but this effect was completely abolished when OCM-1 cells were cultured in Huvec-conditioned medium. When cells were co-cultured on transwell plates and treated with Bevacizumab IL-8 level increased by 30% in OCM-1 culture supernatant (Bev vs CT p=0,12) whereas it was 35% lower in Huvec culture medium (Bev vs CT p<0,05). Conclusions: These data indicate that the UM microenvironment, beside VEGF, can activate IL-8 signalling as an alternative pro-angiogenic pathway. The latter seems to be upregulated in UM cells by anti-VEGF therapy only when they are co-cultured with endothelial cells, thus suggesting that this effect may be dependent on a crosstalk between the two cell types. The decrease in IL-8 concentration, observed in the Huvec chamber of the transwell plates after incubation with Bevacizumab, may be due to a more efficient Il-8 binding by CXCR1 and/or CXCR2 (hypothesis currently tested). Therefore, although preliminary, our results suggest a possible synergic effect for a therapeutic approach combining IL-8 inhibitors with anti-VEGF compounds in UM. Citation Format: Laura Lattanzio, Ilaria Torta, Federica Tonissi, Martino Monteverde, Marco Merlano, Gerard Milano, Cristiana Lo Nigro. Role of IL-8 in uveal melanoma induced angiogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1415. doi:10.1158/1538-7445.AM2013-1415