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.

MARIA FLORENCIA CAYROL ; MARIA MERCEDES DEBERNARDI ; MARIA VICTORIA REVUELTA ; ALEJANDRA PAULAZO ; MARIA NIEVES CALVO VIDAL ; JUDE PHILIP ; HELENA STERLE ; MARIA CELESTE DIAZ FLAQUE ; LEANDRO CERCHIETTI ; GRACIELA CREMASCHI

Buenos Aires

Congreso; Reunión Conjunta de sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica y 9 Sociedades Científicas más

Bexarotene (Bex) is used for the treatment of CTCL and is associatedwith hypothyroidism, so patients concomitantly received THadministration. We found that physiological levels of TH increase theproliferation of CTCL by activating TH membrane receptor, integrinaVb3 (mTR). Here, we determined the influence of TH replacementtherapy on the anti-lymphoma activity of Bex.In standard conditions, Bex decreases the proliferation and viabilityof HuT78 and MJ CTCL cells. To study this mechanism weconducted RNA-sequencing in Bex-treated HuT78 cells (vs. vehicle)and found that Bex up-regulates genes related to cell proliferationand 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 ofBex on CTCL viability. As hypothyroidism is associated with markedimmunosuppression, thus favouring CTCL progression, we determinedthe impact of TH replacement on Bex using a murine TCLmodel of EL4 cells. Once tumors developed, we treated mice withvehicle (Veh), Bex (Bex) and Bex with TH replacement (BexT4+).Bex administration decreased tumor growth being the effect significantlyhigher in the absence of T4 replacement (p