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

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

Mar del Plata

Congreso; Reunión Conjunta SAIC, SAI, SAFIS; 2018

Bexarotene (Bex) is a sintetic rexinoid mostly used for the treatmentof cutaneous T-cell lymphoma. Currently, Bex is being studied asalternative therapy for other types of cancer including different subtypesof T cell lymphomas (TCL). TCL are a heterogeneous groupof aggressive lymphoproliferative disorders. Most TCL patients havepoor prognosis, due to the aggressive clinical course and the lack ofspecific treatments. Tumor growth, including TCL, has a complex relationshipwith immune and endocrine systems, since cytokines andhormones are involved in tumor progression. We recently found thatTH, through the action on its membrane receptor (integrin αVβ3)are required for proliferation of TCL. Paradoxically, Bex is associatedwith hypothyroidism, being patients candidates for replacementtherapy with high doses of TH. The consequences of TH administrationon the activity of Bex are unknown. The aim of this work wasto evaluate Bex action on different subtypes of TCL, distinct fromcutaneous TCL, and how TH could affect the anti-lymphoma activityof this rexinoid.We first evaluated cell viability after 48 hours treatment on humanTCL cells lines representing 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 cells tested(p