Abstract 2650: Angiogenic inhibitors reduce mycosis fungoides cell survival and enhance cell death

Abstract

Cutaneous T-cell lymphomas (CTCL) account for approximately 80% of cases of cutaneous lymphomas. Among CTCL, mycosis fungoides (MF) is the most common and most studied type comprising up to 55% of cases. Three different MF stages are recognized in the following order of pathology evolution: patches, plaques and tumor; MF can progress to tumor stage with involvement of other organs, compromising life due to systemic malignant invasion and immunosuppression. Currently, there are not long-lasting treatment for MF. We aimed to understand if angiogenesis, involved in solid tumor progression, could be involved in MF course. For this, we studied both, MF cell lines (HH, Myla) and skin tissues from MF patients at its different stages including healthy skin, according to ethical approval statements. We evaluated the density of blood vessels in skin from MF patients using staining for CD31 by immunohistochemistry. In HH and Myla cell lines, we have studied the presence of angiogenic receptors by western blot and then we have analyzed the effect of 3 angiogenic inhibitors, axitinib, cabozantinib and sunitinib, on cell survival and cell death. We found that there is an increased number of blood vessels in tumor stage compared with patch stage and healthy skin, and in plaque stage compared with patch stage. In HH and Myla cells that express VEGR2 and c-MET, we noticed that although they are sensitive to the angiogenic inhibitors used, axitinib and specially sunitinib reduced significantly cell survival and enhanced cell death at doses between 5-10 micromolar, at 72 hours. We conclude that the density of blood vessels increases with MF progression and thus that angiogenesis takes place during MF pathophysiology. Furthermore, the fact that angiogenic inhibitors already used in tumor treatment provoke MF cell death and affect MF cell survival, suggests that the use of angiogenic inhibitors could be of great interest for controlling MF progression. Future animal model experiments and clinical trials should reveal the potential of angiogenesis inhibition as a new therapeutical option for MF treatment. Citation Format: Natalia Rendon-Serna, Maeva Dufies, Luis Alfonso Correa-Londono, Olga Maria Bermudez-Munoz, Margarita Maria Velasquez-Lopera, Gilles Pages. Angiogenic inhibitors reduce mycosis fungoides cell survival and enhance cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2650.