Singhal Sunil, Bhojnagarwala Pratik S, O'Brien Shaun, Moon Edmund K, Garfall Alfred L, Rao Abhishek S, Quatromoni Jon G, Stephen Tom Li, Litzky Leslie, Deshpande Charuhas, Feldman Michael D, Hancock Wayne W, Conejo-Garcia Jose R, Albelda Steven M, Eruslanov Evgeniy B
Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Thoracic Surgery, Department of Surgery, Philadelphia VA Medical Center, Philadelphia, PA 19104, USA.
Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Cancer Cell. 2016 Jul 11;30(1):120-135. doi: 10.1016/j.ccell.2016.06.001. Epub 2016 Jun 30.
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 (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-γ and granulocyte-macrophage colony-stimulating factor 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.
基于对小鼠肿瘤模型的研究,粒细胞似乎发挥着促肿瘤作用。然而,关于人类肿瘤相关中性粒细胞(TAN)的表型和功能的数据有限。在此,我们在早期人类肺癌中鉴定出了一部分兼具中性粒细胞和抗原呈递细胞(APC)特征的TAN。这些类似APC的“混合中性粒细胞”源自CD11b(+)CD15(hi)CD10(-)CD16(low)未成熟祖细胞,能够交叉呈递抗原,以及触发和增强抗肿瘤T细胞反应。干扰素-γ和粒细胞-巨噬细胞集落刺激因子是肿瘤中的必需因子,它们通过Ikaros转录因子协同发挥对祖细胞的APC促进作用。总体而言,这些数据证明了人类癌症中存在具有抗肿瘤能力的特殊TAN亚群。