Gliomas are brain tumors characterized by immunosuppression. Immunostimulatory agonistic CD40 antibodies (αCD40) are in clinical development for solid tumors but are yet to be evaluated for glioma. Here, systemic delivery of αCD40 led to cytotoxic T cell dysfunction and impaired the response to immune checkpoint inhibitors in preclinical glioma models. This was associated with an accumulation of suppressive CD11b+ B cells. However, αCD40 also induced tertiary lymphoid structures (TLS). In human glioma, TLS correlated with increased T cell infiltration indicating enhanced immune responses. Our work unveils the pleiotropic effects of αCD40 therapy in glioma, which is of high clinical relevance.

中文翻译：

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激动性CD40抗体疗法可诱导三级淋巴样结构，但会损害对神经胶质瘤免疫检查点封锁的反应

神经胶质瘤是以免疫抑制为特征的脑肿瘤。免疫刺激性激动性CD40抗体（αCD40）正在针对实体瘤的临床开发中，但尚未评估其胶质瘤。在此，在临床前神经胶质瘤模型中，αCD40的全身递送导致细胞毒性T细胞功能障碍，并削弱了对免疫检查点抑制剂的反应。这与抑制性CD11b + B细胞的积累有关。但是，αCD40也会诱导三级淋巴样结构（TLS）。在人脑胶质瘤中，TLS与T细胞浸润增加相关，表明免疫反应增强。我们的工作揭示了αCD40疗法对神经胶质瘤的多效性具有临床意义。