J Clin Invest. 2022 Dec 1;132(23):e165506. doi: 10.1172/JCI165506.
Myeloid-derived suppressor cells (MDSCs) hinder antitumor immunity in multiple cancer types. While brequinar (BRQ), an inhibitor of dihydroorotate dehydrogenase, shows cytotoxicity in hematological malignancy, it has not yet been adapted to attenuate MDSCs by augmenting bone marrow progenitors in breast cancer. In this issue of the JCI, Colligan et al. demonstrate that BRQ restored terminal differentiation of MDSCs. Using in vivo models of immunotherapy-resistant breast cancer, the authors uncovered a mechanism by which BRQ promoted myeloid cell differentiation by limiting their suppressive function and enhancing the efficacy of immune checkpoint blockade therapy. The findings offer insight into the biogenesis of MDSCs, provide an alternative avenue for cancers that remain unresponsive to conventional therapies, and may be extended to future translational studies in patients.
髓源性抑制细胞（MDSCs）在多种癌症类型中阻碍抗肿瘤免疫。虽然二氢乳清酸脱氢酶抑制剂布雷奎纳（BRQ）在血液恶性肿瘤中具有细胞毒性，但它尚未通过增强乳腺癌中的骨髓祖细胞来减轻 MDSCs。在本期 JCI 中，Colligan 等人证明 BRQ 恢复了 MDSC 的终末分化。使用免疫治疗耐药乳腺癌的体内模型，作者揭示了 BRQ 通过限制其抑制功能和增强免疫检查点阻断治疗的疗效来促进髓样细胞分化的机制。这些发现深入了解了 MDSC 的发生机制，为对传统疗法无反应的癌症提供了另一种治疗途径，并可能扩展到未来患者的转化研究中。
