检查点封锁已成为癌症治疗的一线方法，旨在增强针对肿瘤的适应性免疫反应。然而，其临床疗效仅限于一小部分肿瘤类型，这需要探索针对免疫系统另一个主要分支的新策略。其中一种潜在的策略是对先天免疫细胞中的模式识别受体（PRR）途径进行治疗性调节，这在根除肿瘤方面已显示出希望。此前，我们课题组报道了一种来自南极杜维拉菌（Durvillaea antarctica）的高纯度β-1,3/1,6-葡聚糖（BG136）具有全抗肿瘤作用。在本研究中，我们系统地研究了BG136联合抗PD1抗体在MC38同基因肿瘤模型中的体内抗肿瘤活性。综合转录组学和代谢组学分析表明，BG136 通过重新编程肿瘤微环境使其变得更加促炎，从而增强抗 PD1 抗体的抗肿瘤免疫力。此外，还发现先天性和适应性免疫细胞浸润和激活增加，脂质代谢增强，抗坏血酸和醛糖酸代谢减少。这些发现提供了机制见解，支持 BG136 与免疫检查点抑制剂抗体联合使用时的有效抗肿瘤功效。版权所有 © 2024。由 Elsevier B.V. 出版。

Checkpoint blockades have emerged as a frontline approach in cancer management, designed to enhance the adaptive immune response against tumors. However, its clinical efficacy is limited to a narrow range of tumor types, which necessitates the exploration of novel strategies that target another main branch of the immune system. One such potential strategy is the therapeutic modulation of pattern recognition receptors (PRRs) pathways in innate immune cells, which have shown promise in tumor eradication. Previously, a β-1,3/1,6-glucan with high purity from Durvillaea antarctica (BG136) was reported by our group to exhibit pan-antitumor effects. In the current study, we systemically studied the antitumor activity of BG136 in combination with anti-PD1 antibody in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggested that BG136 enhances the antitumor immunity of anti-PD1 antibody by reprogramming the tumor microenvironment to become more proinflammatory. In addition, an increase in innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, and a decreased in ascorbate and aldarate metabolism were also found. These findings provide mechanistic insights that support the potent antitumor efficacy of BG136 when combined with immune checkpoint inhibitor antibodies.Copyright © 2024. Published by Elsevier B.V.