Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Department of Breast Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Laboratory of Cancer Biology, The Key Lab of Biotherapy in Zhejiang Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310020, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Int Immunopharmacol. 2022 Oct;111:109103. doi: 10.1016/j.intimp.2022.109103. Epub 2022 Aug 6.
Neobavaisoflavone (Neo), as a traditional Chinese medicine, is the active ingredient in the herb Psoralea corylifolial and has antitumor activity. Myeloid-derived suppressor cells (MDSCs), which are a heterogeneous population of haematopoietic cells of the myeloid lineage, have been reported to be closely related to the pathogenesis of tumour progression, but whether Neo can regulate MDSC expansion and function remains unclear. Here, we found that Neo could inhibit the expansion and suppressive function of MDSCs by targeting STAT3. Importantly, Neo inhibited the growth of 4T1 and LLC tumours in vivo, as well as lung metastasis of 4T1 tumours in vivo. Furthermore, we identified MDSCs as the direct targets by which Neo attenuated tumour progression. In addition, Neo notably enhanced anti-PD-1 efficacy in anti-PD-1-insensitive 4T1 tumours. Therefore, our study sheds light on the development of Neobased therapeutic strategies against cancer.
新补骨脂异黄酮（Neo）作为一种中药，是补骨脂属植物的活性成分，具有抗肿瘤活性。髓系来源的抑制细胞（MDSCs）是髓系造血细胞的异质性群体，据报道与肿瘤进展的发病机制密切相关，但 Neo 是否能调节 MDSC 的扩增和功能尚不清楚。在这里，我们发现 Neo 可以通过靶向 STAT3 抑制 MDSC 的扩增和抑制功能。重要的是，Neo 抑制了体内 4T1 和 LLC 肿瘤的生长以及 4T1 肿瘤的肺转移。此外，我们确定 MDSCs 是 Neo 减轻肿瘤进展的直接靶标。此外，Neo 显著增强了抗 PD-1 疗效在抗 PD-1 不敏感的 4T1 肿瘤中。因此，我们的研究为基于 Neo 的癌症治疗策略的发展提供了线索。
