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Prepublished online as a Blood First Edition Paper on June 21, 2002; DOI 10.1182/blood-2002-01-0300.
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Blood, 15 August 2002, Vol. 100, No. 4, pp. 1399-1403
IMMUNOBIOLOGY
Immunomodulatory effects of RXR rexinoids: modulation of
high-affinity IL-2R expression enhances susceptibility to
denileukin diftitox
Gullu Gorgun and
Francine Foss
From the Department of Hematology Oncology and
Experimental Therapeutics, Tufts New England Medical Center, Boston,
MA.
Rexinoids binding to both the retinoic acid receptor (RAR) and
retinoid X receptor (RXR) families of rexinoid receptors have demonstrated clinical activity in hematologic malignancies and have
been shown to mediate genes associated with both growth and differentiation. RXR rexinoids have demonstrated efficacy in the treatment of cutaneous T-cell lymphomas, but the mechanism of action is
unclear. We explored the immunomodulatory effects of RAR and RXR
rexinoids in human T- and B-cell leukemia cells and demonstrated that
RXR rexinoids are capable of up-regulating high-affinity interleukin-2
receptor (IL-2R) expression. Exposure to 10 6 to
10 10 M bexarotene or Panretin for 48 hours was associated
with increased expression of both the p55 and p75 subunits of the IL-2R
in T-cell leukemias and p75 in B-cell leukemias. Furthermore, rexinoid
exposure enhanced susceptibility of the cells to denileukin diftitox
fusion toxin-targeting and -intoxicating cells expressing high-affinity IL-2R. These results suggest a rationale for combining rexinoids with
IL-2R-targeted therapies in lymphoid malignancies as well as possibly
in autoimmune diseases.

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