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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.
Cancer cell, 07/2016, Letnik: 30, Številka: 1Journal Article
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+CD15hiCD10−CD16low 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. •Lung tumors accumulate a subset of TANs with a granulocyte and APC hybrid phenotype•APC-like hybrid neutrophils are able to stimulate the anti-tumor T cell responses•IFN-γ and GM-CSF are requisite factors for the development of hybrid neutrophils•Ikaros negatively regulates the development of hybrid neutrophils from progenitors Singhal et al. identify a subset of tumor-associated neutrophils (TANs) that can cross-present tumor antigens and activate anti-tumor T cells in stage I/II human lung cancer. The induction of these hybrid TANs from progenitors requires GM-CSF and IFN-γ and reduction of Ikaros.
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in: SICRIS
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