尽管积极治疗和免疫疗法取得进展，近年来神经胶质瘤患者的生存率并未显着提高。对治疗的有限反应部分归因于免疫抑制性肿瘤微环境，其中调节性 T 细胞 (Treg) 在免疫耐受中发挥着关键作用。在本研究中，我们研究了补体因子 H (FH) 对神经胶质瘤微环境中 Tregs 的影响，发现 FH 是 ICOS 配体。 FH 与这种免疫检查点分子的结合促进了 Tregs 的存活和功能，并诱导 TGF-β (TGF-β) 和 IL-10 的分泌，同时还抑制了 T 细胞增殖。我们进一步证明人类和小鼠神经胶质瘤中的癌细胞直接产生 FH。数据库调查显示，FH 表达上调与 Tregs 的存在相关，并与神经胶质瘤患者的较差预后相关。我们在小鼠模型中证实了 FH 对神经胶质瘤发育的影响，其中 FH 敲低与 ICOS Tregs 数量减少相关，并表现出延长生存的趋势 (p=0.064)。由于 Tregs 的积累代表了一个有前途的预后和治疗靶标，因此在评估神经胶质瘤免疫疗法的有效性和耐药性时应考虑评估 FH 表达。

The survival rate of glioma patients has not significantly increased in recent years despite aggressive treatment and advances in immunotherapy. The limited response to treatments is partially attributed to the immunosuppressive tumor microenvironment, where regulatory T cells (Tregs) play a pivotal role in immunological tolerance. In this study, we investigated the impact of complement factor H (FH) on Tregs within the glioma microenvironment and found that FH is an ICOS ligand. The binding of FH to this immune checkpoint molecule promoted the survival and function of Tregs and induced the secretion of TGF-beta (TGF-β) and IL-10, while also suppressing T-cell proliferation. We further demonstrated that cancer cells in human and mouse gliomas directly produce FH. Database investigations revealed that upregulation of FH expression was associated with the presence of Tregs and correlated with worse prognosis for glioma patients. We confirmed the effect of FH on glioma development in a mouse model, where FH knockdown was associated with decrease in number of ICOS+ Tregs and demonstrated a tendency of prolonged survival (p=0.064). Since the accumulation of Tregs represents a promising prognostic and therapeutic target, evaluating FH expression should be considered when assessing the effectiveness of and resistance to immunotherapies against glioma.