Upon heterodimerizing with other nuclear receptors, retinoid X receptors (RXR) act as ligand-dependent transcription factors, regulating transcription of critical signaling pathways that impact numerous hallmarks of cancer. By controlling both inflammation and immune responses, ligands that activate RXR can modulate the tumor microenvironment. Several small molecule agonists of these essential receptors have been synthesized. Historically, RXR agonists were tested for inhibition of growth in cancer cells, but more recent drug discovery programs screen new molecules for inhibition of inflammation or activation of immune cells. Bexarotene is the first successful example of an effective therapeutic that molecularly targets RXR; this drug was approved to treat cutaneous T cell lymphoma and is still used as a standard of care treatment for this disease. No additional RXR agonists have yet achieved FDA approval, but several promising novel compounds are being developed. In this review, we provide an overview of the multiple mechanisms by which RXR signaling regulates inflammation and tumor immunity. We also discuss the potential of RXR-dependent immune cell modulation for the treatment or prevention of cancer and concomitant challenges and opportunities.

在与其他核受体异二聚化后，类视黄醇 X 受体 （RXR） 充当配体依赖性转录因子，调节影响癌症众多标志的关键信号通路的转录。通过控制炎症和免疫反应，激活 RXR 的配体可以调节肿瘤微环境。已经合成了这些必需受体的几种小分子激动剂。从历史上看，RXR 激动剂被测试以抑制癌细胞的生长，但最近的药物发现计划筛选了抑制炎症或激活免疫细胞的新分子。贝沙罗汀是分子靶向 RXR 的有效治疗药物的第一个成功例子;这种药物被批准用于治疗皮肤 T 细胞淋巴瘤，并且仍然被用作这种疾病的标准护理治疗。目前还没有其他 RXR 激动剂获得 FDA 批准，但几种有前途的新型化合物正在开发中。在这篇综述中，我们概述了 RXR 信号调节炎症和肿瘤免疫的多种机制。我们还讨论了 RXR 依赖性免疫细胞调节治疗或预防癌症的潜力以及随之而来的挑战和机遇。