Beclin-1 as a neutrophil-specific immune checkpoint.
Beclin-1 as a neutrophil-specific immune checkpoint.
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DOI：
10.1172/jci132534
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
Yu-Lin Su;M. Kortylewski
中科院分区：
文献类型：
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作者：
Yu-Lin Su;M. Kortylewski
中性粒细胞是早期伤口愈合和炎症调节剂，由于功能可塑性，可以采用促或抗肿瘤功能。直到最近，beclin-1还是一种主要以其作为自噬关键调节剂的作用而闻名的蛋白质。在本期JCI中，Tan等人描述了beclin-1条件性髓样细胞特异性缺失对小鼠的影响，其中免疫刺激导致超敏中性粒细胞。这些中性粒细胞的慢性促炎作用触发自发性B细胞恶性肿瘤的发展。这种致瘤作用主要由IL-21和CD 40信号传导介导，导致致耐受性分子如IL-10和PD-L1的上调。作者接着检查了来自淋巴恶性肿瘤患者的样本，结果显示嗜中性粒细胞中的beclin-1表达与前B细胞白血病/淋巴瘤呈正相关。总的来说，这项研究提供了一个优雅的模型，嗜中性粒细胞驱动的致癌作用，并确定了潜在的目标免疫治疗的B细胞恶性肿瘤。
Neutrophils are early wound healing and inflammation regulators that, due to functional plasticity, can adopt either pro- or antitumor functions. Until recently, beclin-1 was a protein known mainly for its role as a critical regulator of autophagy. In this issue of the JCI, Tan et al. describe the effects of the beclin-1 conditional myeloid cell-specific deletion in mice, in which immunostimulation resulted in hypersensitive neutrophils. The chronic proinflammatory effect of these neutrophils triggered spontaneous B cell malignancies to develop. Such tumorigenic effects were mediated primarily by IL-21 and CD40 signaling, leading to the upregulation of tolerogenic molecules, such as IL-10 and PD-L1. The authors went on to examine samples derived from patient lymphoid malignancies and showed that beclin-1 expression in neutrophils positively correlated with pre-B cell leukemia/lymphoma. Overall, the study provides an elegant model for neutrophil-driven carcinogenesis and identifies potential targets for immunotherapy of B cell malignancies.