Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer.
Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer.
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DOI：
10.1016/j.ccell.2016.06.001
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发表时间：
2016-07-11
期刊：
影响因子：
50.3
通讯作者：
Eruslanov EB
中科院分区：
文献类型：
--
作者：
Singhal S;Bhojnagarwala PS;O'Brien S;Moon EK;Garfall AL;Rao AS;Quatromoni JG;Stephen TL;Litzky L;Deshpande C;Feldman MD;Hancock WW;Conejo-Garcia JR;Albelda SM;Eruslanov EB
基于对小鼠肿瘤模型的研究，粒细胞似乎起着促进肿瘤的作用。然而，关于人类肿瘤相关中性粒细胞（TANs）的表型和功能的数据有限。在这里，我们确定了在早期人类肺癌中表现出中性粒细胞和抗原呈递细胞（APC）特征的TANs亚群。这些apc样的“杂交中性粒细胞”源自CD11b+CD15hiCD10−CD16low未成熟祖细胞，能够交叉呈递抗原，并触发和增强抗肿瘤T细胞反应。IFN-γ和GM-CSF是肿瘤中必不可少的因子，通过Ikaros转录因子协同作用，对祖细胞发挥apc促进作用。总的来说，这些数据证明了在人类癌症中存在一个具有抗肿瘤能力的特化TAN亚群。
Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APC) in early-stage human lung cancer. These APC-like “hybrid neutrophils”, which originate from CD11b+CD15hiCD10−CD16low immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. IFN-γ and GM-CSF are requisite factors in the tumor that working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer.