CTCL

AACR 2017 poster 3132/21 – Inhibition of the integrin αVβ3 improves the effect of bexarotene in the treatment of Cutaneous T-Cell Lymphoma

At the American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA, on Tuesday 4th April, a poster session titled “Molecular Medicine” took place.

One of the posters on display (3132 / 21) was titled “Inhibition of the integrin αVβ3 improves the effect of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL)” by Florencia Cayrol from the Biomedical Research Institute, Buenos Aires, Argentina, and colleagues.

The group aimed to evaluate how the anti-lymphoma activity of bexarotene (BEX) is affected by activation of the classical nuclear Thyroid Hormone Receptor (TR) and the membrane receptor integrin αVβ3 during Thyroid Hormone (TH) replacement therapy.

Key Highlights:
  • BEX decreased viability of HuT78 and MJ CTCL cells
  • Physiological concentration of THs decreased the anti-lymphoma effect of BEX by 25–60% and 20–50% on HuT78 and MJ cells
  • In a mouse allograft TCL model, BEX plus TH reduced the direct anti-lymphoma effect of BEX but enhanced immune infiltration
  • RNA-sequencing in HuT78 cells treated with BEX-T4 in presence of siRNA for TR, αVβ3, or controls; genes involved in apoptosis, angiogenesis, and IL6-JAK-STAT3 signaling were differentially expressed in si-αVβ3 vs the others
  • Pharmacologic inhibition of integrin αVβ3 by cilengitide increased the anti-lymphoma effect of BEX in CTCL cells by 15–30%; was higher in HuT78 3D organoid model

The effect of cilengitide on the efficacy of BEX is currently being analyzed in murine CTCL models. The poster was concluded by stating that these data indicate that, even in the present of TH replacement therapy, inhibition of the integrin αVβ3 improves the efficacy of bexarotene in CTCL.

Reference:
  1. Cayrol F. et al. Inhibition of the integrin αVβ3 improves the effect of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) [Poster]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Poster nr [3132 / 21].