Exciting progress in the field of cancer immunotherapy has renewed the urgency of the need for basic studies of immunoregulation in both adaptive cell lineages and innate cell lineages. Here we found a central role for major histocompatibility complex (MHC) class I in controlling the phagocytic function of macrophages. Our results demonstrated that expression of the common MHC class I component β₂-microglobulin (β2M) by cancer cells directly protected them from phagocytosis. We further showed that this protection was mediated by the inhibitory receptor LILRB1, whose expression was upregulated on the surface of macrophages, including tumor-associated macrophages. Disruption of either MHC class I or LILRB1 potentiated phagocytosis of tumor cells both in vitro and in vivo, which defines the MHC class I-LILRB1 signaling axis as an important regulator of the effector function of innate immune cells, a potential biomarker for therapeutic response to agents directed against the signal-regulatory protein CD47 and a potential target of anti-cancer immunotherapy.

中文翻译：

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抑制受体LILRB1与I类MHC的结合可抑制巨噬细胞，是癌症免疫疗法的目标。

癌症免疫治疗领域令人振奋的进展重新表明了对适应性细胞谱系和先天细胞谱系的免疫调节基础研究的紧迫性。在这里，我们发现主要组织相容性复合体（MHC）I类在控制巨噬细胞的吞噬功能中起着核心作用。我们的结果表明共同类MHC的表达I分量β ₂癌细胞产生的β-微球蛋白（β2M）可直接保护它们免于吞噬作用。我们进一步表明，这种保护作用是由抑制性受体LILRB1介导的，其表达在包括肿瘤相关巨噬细胞在内的巨噬细胞表面被上调。干扰MHC I类或LILRB1增强了肿瘤细胞在体内和体外的吞噬作用，这将MHC I-LILRB1信号转导轴定义为先天免疫细胞效应功能的重要调节剂，是潜在的治疗性生物标志物针对信号调节蛋白CD47的抗癌药物和抗癌免疫疗法的潜在靶标。