Programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) checkpoint blocking antibodies have been shown to be a powerful immune checkpoint blockade (ICB) therapy for patients with cancer. However, patients quickly develop resistance to immunotherapy. β-glucan, an immune adjuvant, has been found to stimulate innate and adaptive immune responses. In this study, we assessed the use of whole glucan particle (WGP) β-glucan in combination with PD-1/PD-L1-blocking antibodies to slow down the resistance to immunotherapy. Results from a tumor mouse model demonstrated that administration of WGP β-glucan plus PD-1/PD-L1-blocking antibodies led to increased recruitment of immune-associated cells, improved regulation of the balance between T-cell activation and immune tolerance, and delayed tumor progression. This combination therapy was also found to improve progression-free survival in patients with advanced cancer who had previously discontinued anti-PD-1/PD-L1 because of disease progression. These findings suggest that β-glucan could be used as an immune adjuvant to reverse anti-PD-1/PD-L1 resistance by regulating the immune system.

中文翻译：

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β-葡聚糖联合 PD-1/PD-L1 检查点阻断剂用于晚期癌症患者的免疫治疗。

程序性死亡 1 (PD-1)/PD-配体 1 (PD-L1) 检查点阻断抗体已被证明是针对癌症患者的强大免疫检查点阻断 (ICB) 疗法。然而，患者很快就会对免疫疗法产生耐药性。β-葡聚糖是一种免疫佐剂，已被发现可刺激先天性和适应性免疫反应。在这项研究中，我们评估了全葡聚糖颗粒 (WGP) β-葡聚糖与 PD-1/PD-L1 阻断抗体联合使用以减缓对免疫疗法的抵抗力。来自肿瘤小鼠模型的结果表明，给予 WGP β-葡聚糖加 PD-1/PD-L1 阻断抗体可增加免疫相关细胞的募集，改善 T 细胞活化和免疫耐受之间平衡的调节，以及延缓肿瘤进展。还发现这种联合疗法可以提高先前因疾病进展而停用抗 PD-1/PD-L1 的晚期癌症患者的无进展生存期。这些发现表明，β-葡聚糖可用作免疫佐剂，通过调节免疫系统来逆转抗 PD-1/PD-L1 抗性。