美国约翰霍普金斯大学医学院Masanobu Komatsu小组研究发现STING和淋巴毒素β受体同时激活可诱导三级淋巴结构中的B细胞反应，从而增强抗肿瘤免疫。相关论文于2025年9月2日发表在《自然—免疫学》杂志上。

本研究表明，同时激活先天免疫效应物STING和淋巴毒素β受体（LTβR），导致CD8⁺ T细胞依赖性肿瘤抑制，同时诱导肿瘤中内皮小静脉的高度发育和生发中心样B细胞反应，以T细胞依赖性的方式产生功能性TLS。在新辅助治疗中，STING和LTβR的激动剂激活可以有效地免疫小鼠，使其免于肿瘤复发，从而获得长期生存。单独激活STING不足以诱导含B细胞的TLS或引起长期的治疗效果。

然而，当与LTβR激活联合使用时，它提高了具有B细胞扩增和成熟的TLS对产生IgG的长寿浆细胞和记忆细胞的适应性，增加了CD4⁺ T细胞募集和记忆CD8⁺ T细胞扩增，并改变了T_H2/T_H17平衡，从而增强了对肿瘤的体液和细胞免疫。这些发现提示了一种同时激活STING和淋巴毒素途径的治疗方法。

据了解，富含B细胞的三级淋巴结构（TLS）与癌症患者良好的预后和对免疫治疗的积极反应有关。

附：英文原文

Title: Simultaneous STING and lymphotoxin-β receptor activation induces B cell responses in tertiary lymphoid structures to potentiate antitumor immunity

Author: Sawada, Junko, Kikuchi, Yasuhiro, Duah, Maxwell, Herrera, Jose Luis, Kanamori, Fumiaki, Csomos, Krisztian, Stansel, Tomoko, Hiraoka, Nobuyoshi, Yoshida, Masayuki, Walter, Jolan, Ware, Carl F., Komatsu, Masanobu

Issue&Volume: 2025-09-02

Abstract: B cell-rich tertiary lymphoid structures (TLS) are associated with favorable prognosis and positive response to immunotherapy in cancer. Here we show that simultaneous activation of innate immune effectors, STING and lymphotoxin-β receptor (LTβR), results in CD8+ T cell-dependent tumor suppression while inducing high endothelial venule development and germinal center-like B cell responses in tumors to generate functional TLS in a T cell-dependent manner. In a neoadjuvant setting, activation of STING and LTβR by their agonists effectively immunized mice against tumor recurrence, leading to long-term survival. STING activation alone was insufficient for inducing B cell-containing TLS or eliciting long-term therapeutic effects. However, when combined with LTβR activation, it improved the fitness of TLS with B cell expansion and maturation to IgG-producing long-lived plasma cells and memory cells, increased CD4+ T cell recruitment and memory CD8+ T cell expansion, and shifted the TH2/TH17 balance, resulting in the potentiation of humoral and cellular immunity against tumors. These findings suggest a therapeutic approach of simultaneously activating STING and lymphotoxin pathways.

DOI: 10.1038/s41590-025-02259-8

Source: https://www.nature.com/articles/s41590-025-02259-8