免疫检查点阻断（ICB）疗法在癌症治疗中取得了前所未有的进展。然而，ICB 治疗的反应仅限于一小部分患者。迫切需要开发 ICB 增敏剂来改善癌症免疫治疗的结果。小檗碱（BBR）是从小檗、黄连、黄柏等多种药用植物中分离出来的一种著名的植物化学化合物，具有抑制癌细胞增殖、侵袭和转移的能力。在本研究中，我们研究了 BBR 是否可以增强 ICB 对黑色素瘤的治疗效果，并探讨了其中的潜在机制。结果表明，BBR可以使ICB增敏，抑制肿瘤生长，提高小鼠的存活率。此外，BBR 部分通过抑制 NQO1 活性来刺激细胞内 ROS 产生，从而诱导黑色素瘤中的免疫原性细胞死亡 (ICD)，提高损伤相关分子模式 (DAMP) 的水平，并随后在体外和体内激活 DC 细胞和 CD8 T 细胞体内。总之，BBR 是一种新型 ICD 诱导剂。 BBR 可以增强 ICB 对黑色素瘤的治疗效果。这些效应部分是通过抑制 NQO1 和 ROS 激活来介导的。版权所有 © 2024。由 Elsevier B.V. 出版。

Unprecedented progress in immune checkpoint blockade (ICB) therapy has been made in cancer treatment. However, the response to ICB therapy is limited to a small subset of patients. The development of ICB sensitizers to improve cancer immunotherapy outcomes is urgently needed. Berberine (BBR), a well-known phytochemical compound isolated from many kinds of medicinal plants such as Berberis aristata, Coptis chinensis, and Phellondendron chinense Schneid, has shown the ability to inhibit the proliferation, invasion and metastasis of cancer cells. In this study, we investigated whether BBR can enhance the therapeutic benefit of ICB for melanoma, and explored the underlying mechanisms involved. The results showed that BBR could sensitize ICB to inhibit tumor growth and increased the survival rate of mice. Moreover, BBR stimulated intracellular ROS production partially by inhibiting NQO1 activity, which induced immunogenic cell death (ICD) in melanoma, elevated the levels of damage-associated molecular patterns (DAMPs), and subsequently activated DC cells and CD8 + T cells in vitro and in vivo. In conclusion, BBR is a novel ICD inducer. BBR could enhance the therapeutic benefit of ICB for melanoma. These effects were partially mediated through the inhibition of NQO1 and ROS activation.Copyright © 2024. Published by Elsevier B.V.