Unique pattern of neutrophil migration and function during tumor progression.

Autor: Patel S; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA.; Bristol-Myers Squibb, Lawrenceville, NJ, USA., Fu S; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA.; Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China., Mastio J; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA., Dominguez GA; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA.; ITUS Corporation, San Jose, CA, USA., Purohit A; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA., Kossenkov A; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA., Lin C; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA., Alicea-Torres K; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA., Sehgal M; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA., Nefedova Y; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA., Zhou J; Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China., Languino LR; Sidney Kimmel Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Clendenin C; University of Pennsylvania School of Medicine, Philadelphia, PA, USA., Vonderheide RH; University of Pennsylvania School of Medicine, Philadelphia, PA, USA., Mulligan C; Helen F Graham Cancer Center at Christiana Care Health System, Wilmington, DE, USA., Nam B; Helen F Graham Cancer Center at Christiana Care Health System, Wilmington, DE, USA., Hockstein N; Helen F Graham Cancer Center at Christiana Care Health System, Wilmington, DE, USA., Masters G; Helen F Graham Cancer Center at Christiana Care Health System, Wilmington, DE, USA., Guarino M; Helen F Graham Cancer Center at Christiana Care Health System, Wilmington, DE, USA., Schug ZT; Molecular & Cellular Oncogenesis Programs, Wistar Institute, Philadelphia, PA, USA., Altieri DC; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA., Gabrilovich DI; Immunology, Microenvironment, and Metastasis, Wistar Institute, Philadelphia, PA, USA. dgabrilovich@wistar.org.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2018 Nov; Vol. 19 (11), pp. 1236-1247. Date of Electronic Publication: 2018 Oct 15.
DOI: 10.1038/s41590-018-0229-5
Abstrakt: Although neutrophils have been linked to the formation of the pre-metastatic niche, the mechanism of their migration to distant, uninvolved tissues has remained elusive. We report that bone marrow neutrophils from mice with early-stage cancer exhibited much more spontaneous migration than that of control neutrophils from tumor-free mice. These cells lacked immunosuppressive activity but had elevated rates of oxidative phosphorylation and glycolysis, and increased production of ATP, relative to that of control neutrophils. Their enhanced spontaneous migration was mediated by autocrine ATP signaling through purinergic receptors. In ectopic tumor models and late stages of cancer, bone marrow neutrophils demonstrated potent immunosuppressive activity. However, these cells had metabolic and migratory activity indistinguishable from that of control neutrophils. A similar pattern of migration was observed for neutrophils and polymorphonuclear myeloid-derived suppressor cells from patients with cancer. These results elucidate the dynamic changes that neutrophils undergo in cancer and demonstrate the mechanism of neutrophils' contribution to early tumor dissemination.
Databáze: MEDLINE
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