Bexarotene treatment for cutaneous T cell lymphoma (CTCL): implications of thyroid hormone (TH) replacement in the anti-lymphoma activity and in the antitumoral immune response.

CAYROL F; DEBERNARDI M; REVUELTA MV; PAULAZO MA; CALVO-VIDAL MN; PHILLIP J; STERLE HA; DIAZ FLAQUE MARIA MC; CERCHIETTI LC; CREMASCHI GA

Congreso; Reunión conjunta de sociedades biomédicas; 2017

Bexarotene (Bex) is used for the treatment of CTCL and is associated with hypothyroidism, so patients concomitantly received TH administration. We found that physiological levels of TH increase the proliferation of CTCL by activating TH membrane receptor, integrin V3 (mTR). Here, we determined the influence of TH replacement therapy on the anti-lymphoma activity of Bex.In standard conditions, Bex decreases the proliferation and viability of HuT78 and MJ CTCL cells. To study this mechanism we conducted RNA-sequencing in Bex-treated HuT78 cells (vs. vehicle) and found that Bex up-regulates genes related to cell proliferation and differentiation (REL, CCND1) and to immunity (TBX21, IFNG). This suggests that Bex treatment could impact in antitumor immunity. In TH-depleted culture conditions we observed a higher effect of Bex on CTCL viability. As hypothyroidism is associated with marked immunosuppression, thus favouring CTCL progression, we determined the impact of TH replacement on Bex using a murine TCL model of EL4 cells. Once tumors developed, we treated mice with vehicle (Veh), Bex (Bex) and Bex with TH replacement (BexT4+). Bex administration decreased tumor growth being the effect significantly higher in the absence of T4 replacement (p