免疫检查点抑制剂对以预先存在的 T 细胞浸润和干扰素 (IFN) 信号传导为特征的发炎肿瘤的疗效显着高于对非发炎“冷”肿瘤的疗效，后者通常对免疫治疗具有抵抗力。癌症免疫疗法 bexmarilimab 可抑制清道夫受体 Clever-1，释放巨噬细胞免疫抑制并激活适应性免疫，已在部分晚期实体恶性肿瘤患者中显示出治疗效果。然而，决定个体患者 bexmarilimab 治疗结果的机制尚不清楚。在这里，我们使用单细胞 RNA 测序表征了卵巢癌腹水巨噬细胞离体中的 bexmarilimab 反应，并证明了 bexmarilimab 治疗后 IFN 信号传导和 CXCL10 分泌增加。我们进一步表明，bexmarilimab 在低基线 IFN 信号传导的巨噬细胞中最有效，因为慢性 IFNγ 启动消除了 bexmarilimab 诱导的 TNFα 释放。这些结果突出了一种针对免疫冷肿瘤并增加其随后对免疫检查点抑制剂做出反应的可能性的方法。

Immune checkpoint inhibitors show substantially greater efficacy in inflamed tumors characterized by pre-existing T cell infiltration and interferon (IFN) signaling than in non-inflamed, "cold", tumors, which often remain immunotherapy resistant. The cancer immunotherapy bexmarilimab, which inhibits the scavenger receptor Clever-1 to release macrophage immunosuppression and activate adaptive immunity, has shown treatment benefit in subsets of patients with advanced solid malignancies. However, the mechanisms that determine bexmarilimab therapy outcome in individual patients are unknown. Here we characterized bexmarilimab response in ovarian cancer ascites macrophages ex vivo using single-cell RNA-sequencing and demonstrated increased IFN signaling and CXCL10 secretion following bexmarilimab treatment. We further showed that bexmarilimab was most efficacious in macrophages with low baseline IFN signaling, as chronic IFNγ priming abolished bexmarilimab-induced TNFα release. These results highlight an approach to target immunologically cold tumors and to increase the likelihood of their subsequent response to immune checkpoint inhibitors.