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

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

Congreso; Reunion Conjunta de Sociedades de Biociencias 2018; 2018

Bexarotene(Bex) is a sintetic rexinoid mostly used for the treatment of cutaneous T-celllymphoma. Currently, Bex is being studied as alternative therapy for othertypes of cancer including different subtypes of T cell lymphomas (TCL). TCL area heterogeneous group of aggressive lymphoproliferative disorders. Most TCLpatients have poor prognosis, due to the aggressive clinical course and thelack of specific treatments. Tumor growth, including TCL, has a complexrelationship with immune and endocrine systems, since cytokines and hormonesare involved in tumor progression. We recently found that TH, through theaction on its membrane receptor (integrin αVβ3) are required for proliferationof TCL. Paradoxically, Bex is associated with hypothyroidism, being patientscandidates for replacement therapy with high doses of TH. The consequences ofTH administration on the activity of Bex are unknown. The aim of this work wasto evaluate Bex action on different subtypes of TCL, distinct from cutaneousTCL, and how TH could affect the anti-lymphoma activity of this rexinoid. Wefirst evaluated cell viability after 48 hours treatment on human TCL cellslines representing different subtypes and origins; CUTLL1 (immature) and,OCI-Ly12, OCI-Ly13.2 and MAC2a (mature). We treated them with increasingconcentrations of Bex (0-80 μM) and found a significantly decrease in cellviability in all cells tested (p<.0.01 vs vehicle). Then, we evaluated onOCI-Ly12 and OCI-Ly13.2 cells Bex activity in the presence or absence ofphysiological concentrations of TH. After treatment Bex decreased viability andinduce apoptosis in all cell lines, but in the presence of TH both effectsdecreased by 20-40% (p<0.05 vs Bex alone). These resultsprovides us the knowledge bases that allow us to continue studying newtherapeutic approaches for this pathology; and in the future, may help toimprove the response to treatment of   TCL patients.