大麻二酚通过 cGAS-STING 通路上调三阴性乳腺癌细胞中的 PD-L1 表达,从而增强 Atezolizumab 的疗效。
Cannabidiol enhances Atezolizumab efficacy by upregulating PD-L1 expression via the cGAS-STING pathway in triple-negative breast cancer cells.
发表日期:2024 Sep 03
作者:
Bu Gyeom Kim, Bo Ram Kim, Dae Yeong Kim, Woo Young Kim, Sanghee Kang, Sun Il Lee, Sang Cheul Oh
来源:
Cellular & Molecular Immunology
摘要:
三阴性乳腺癌(TNBC)患者的治疗依赖于细胞毒疗法。目前,atezolizumab 和化疗可以联合治疗 TNBC 患者。然而,这种方法并非对所有对 atezolizumab 反应性低的患者有效。由于缺乏替代治疗选择,迫切需要新的抗癌药物来增强 atezolizumab 对 TNBC 的反应性。最近的策略集中在调节程序性死亡配体 1 (PD-L1) 的表达或通过将抗癌药物与免疫检查点抑制剂 (ICIs) 相结合来增强免疫反应激活。大麻二酚 (CBD) 是一种从大麻植物中提取的大麻素成分,据报道具有抗癌治疗潜力,因为它能够诱导肿瘤细胞凋亡,同时避免正常细胞的细胞毒性。先前的研究已经证明 CBD 对各种癌细胞类型细胞凋亡的影响。然而,CBD 作为免疫调节剂在调节 PD-L1 表达和抗癌免疫反应中的潜在作用仍有待探索。在这项研究中,我们发现 CBD 刺激 TNBC 细胞中的 PD-L1 表达,从而显着诱导 CBD 介导的 cGAS-STING 通路激活。综上所述,我们在体外和体内实验中证明了 CBD 和抗 PD-L1 抗体的组合可增强抗癌免疫反应。我们的研究结果确定了 CBD 在 TNBC 细胞中调节 PD-L1 的机制,并表明 CBD 可能是在 TNBC 患者中开发与 ICI 的新组合策略的潜在候选者。
The treatment of patients with triple negative breast cancer (TNBC) relies on cytotoxic therapy. Currently, atezolizumab and chemotherapy can be combined in patients with TNBC. However, this approach is not effective for all patients with low reactivity to atezolizumab. As there is a lack of alternative treatment options, new anti-cancer drugs are urgently needed to enhance atezolizumab reactivity against TNBC. Recent strategies have focused on regulating the expression of programmed death-ligand 1 (PD-L1) or enhancing immune response activation by combining anti-cancer drugs with immune checkpoint inhibitors (ICIs). Cannabidiol (CBD), a cannabinoid component derived from the cannabis plant, has been reported to have anti-cancer therapeutic potential because of its capacity to induce apoptotic cell death in tumor cells while avoiding cytotoxicity in normal cells. Previous studies have demonstrated the effects of CBD on apoptosis in various cancer cell types. However, the potential role of CBD as an immune modulator in the regulation of PD-L1 expression and anti-cancer immune responses remains to be explored. In this study, we found that CBD stimulated PD-L1 expression in TNBC cells, which significantly induced the CBD-mediated cGAS-STING pathway activation. Taken together, we demonstrated that the combination of CBD and anti-PD-L1 antibody enhances the anti-cancer immune response in vitro and in vivo experiments. Our findings identified the mechanism of PD-L1 regulation by CBD in TNBC cells and suggested that CBD could be a potential candidate for the development of new combinatorial strategies with ICIs in TNBC patients.