Biological effects of bexarotene in cutaneous T-cell lymphoma

Objective: To determine the effects of bexarotene on malignant T cells isolated from the peripheral blood of patients with the leukemic variant of cutaneous T-cell lymphoma (Sezary syndrome). Design, Setting, and Participants: Peripheral blood mononuclear cells from 9 patients with Sezary syndrome and a high burden of circulating malignant T cells (>50% of peripheral blood mononuclear cells) and 6 healthy volunteers underwent evaluation at a university medical center, to test the effects of bexarotene on T cells. Main Outcome Measures: The capacity of bexarotene to induce apoptosis and its effects on T-cell cytokine production from peripheral blood lymphocytes isolated from patients with Sezary syndrome. Results: Bexarotene produced dose-dependent apoptosis of peripheral blood T cells from patients with Sezary syndrome. The T cells from approximately two thirds of patients were consistently sensitive to bexarotene, whereas those from the remaining one third of patients were consistently resistant to the apoptotic effects of bexarotene. Bexarotene inhibited mitogen-induced interleukin 4 production by the peripheral blood cells of patients with Sezary syndrome, and this effect correlated with sensitivity of patients' cells to apoptosis. In contrast to the retinoic acid receptor-specific retinoid, all-trans retinoic acid, bexarotene does not induce the augmentation of interferon gamma production. Conclusions: Bexarotene induces apoptosis of malignant T cells from patients with Sezary syndrome, but the cells from a proportion of patients are resistant to the apoptotic effects. Interleukin 4 production, which can play a role in the systemic immunosuppression that characterizes advancing Sezary syndrome, may be inhibited by bexarotene.