Possible Interaction: Tretinoin and Aldesleukin

“We have demonstrated, in a … study, that administering low-dose interleukin-2 (IL-2) and … retinoic acid ( RA ), there was a significant improvement of the immune function, with low toxicity, in PTS with advanced … had been treated with aggressive surgery and chemotherapy (Clin Cancer Res 7: 1251-1257, 2001).”

“13-cis retinoic acid (RA) has immunomodulatory properties, potentially synergistic with IL-2.”

“After a median follow-up time of 31 months there was a statistically significant improvement in the number of total lymphocytes, T4/T8 ratio and NK after IL-2 and RA therapy.”

“The authors additionally report that the presence of IL-2 during in vitro generation of Treg confers resistance to Th17 conversion and that IL-2 cooperates with retinoic acid (RA) to maintain Foxp3 expression following stimulation under Th17-polarizing conditions.”

“In fact, DC-derived retinoic acid RA ) helps the conversion process by counteracting the negative impact of costimulation.”

“Thus, RA may interfere with the negative impact of costimulation on Treg conversion by interfering with the generation and/or function of AP-1.”

“A second observation is that ATRA treated cells are, only apparently, less sensitive to lysis by lymphocytes activated by IL-2 , as determined by means of a standard 51Cr release assay.”

“In transfection studies using a luciferase reporter construct expressing the IL-2 promoter or a tandem repeat of AP-1 or NF-κB, the inhibitory effect of ATRA on the IL-2 promoter and AP-1 construct was confirmed at the transcriptional level.”

“Hypoxia and retinoic acid (RA) may also induce interleukin-2 (IL-2) receptor expression, and thus we evaluated if RA and IL-2 receptor-targeted therapy are indicated in hypoxic HCCs.”

“ ATRA enhanced the production of IL-2 stimulated by TPA, but suppressed that stimulated by PHA.”

“These results suggest that ATRA affects the production of IL-2 by T-lymphocytes in a stimulus-dependent manner.”

“Thus, at concentrations as low as 0.1 nM, RA enhanced the division of normal human T lymphocytes that were simultaneously stimulated with anti-CD3 mAbs and saturating concentrations of IL-2.”

“Together, these results suggest that retinoic acid inhibits spontaneous apoptosis of activated T lymphocytes through a RAR-dependent increase in IL-2 production.”