Rexinoids for the treatment of T cell lymphoma (TCL): implications of thyroid hormones (TH) in bexarotene anti-lymphoma activity

DEBERNARDI MM; CAYROL F; DÍAZ ALBUJA JA; STERLE HA; ROSEMBLIT C; CREMASCHI GA

Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018

Bexarotene (Bex) is a sintetic rexinoid mostly used for the treatment of cutaneous T-cell lymphoma. Currently, Bex is being studied as alternative therapies for other typesof cancer including different subtypes of T cell lymphomas (TCL). TCL are aheterogeneous group of aggressive lymphoproliferative disorders. Most TCL patientshave poor prognosis, due to the aggressive clinical course and the lack of specifictreatments. Tumor growth, including TCL, has a complex relationship with immune andendocrine systems since cytokines and hormones, are involved in tumor progression.We recently found that TH, through the action on its membrane receptor (integrinV3) are required for proliferation of TCL. Paradoxically, Bex is associated withhypothyroidism, being patients candidates for replacement therapy with high doses ofTH. The consequences of TH administration on the activity of Bex are unknown. Theaim of this work was to evaluate Bex action on different subtypes of TCL, distinct fromcutaneous TCL, and how TH could affect the anti-lymphoma activity of this rexinoid.We first evaluated cell viability after 48 hours treatment on human TCL cells linesrepresenting different subtypes and origins; CUTLL1 (immature) and, OCI-Ly12, OCI-Ly13.2 and MAC2a (mature). We treated them with increasing concentrations of Bex(0-80 μM) and found a significantly decrease in cell viability in all cell tested (p