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.

中文翻译：

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Beclin-1作为中性粒细胞特异性免疫检查点。

中性粒细胞是伤口的早期愈合和炎症调节因子，由于功能可塑性，可以发挥促癌或抗肿瘤作用。直到最近，beclin-1还是一种蛋白质，主要由于其作为自噬的关键调节剂而闻名。在JCI的这一期中，Tan等人。的文献描述了beclin-1条件性髓样细胞特异性缺失在小鼠中的作用，其中免疫刺激导致过敏性中性粒细胞增高。这些中性粒细胞的慢性促炎作用触发了自发性B细胞恶性肿瘤的发展。此类致瘤作用主要由IL-21和CD40信号传导介导，导致致耐受性分子（例如IL-10和PD-L1）的上调。这组作者继续检查了来自患者淋巴恶性肿瘤的样本，并表明中性粒细胞中的beclin-1表达与B细胞前白血病/淋巴瘤呈正相关。总体而言，该研究为嗜中性粒细胞驱动的致癌作用提供了一个优雅的模型，并确定了B细胞恶性肿瘤免疫治疗的潜在靶标。