title: Aging and cancer: The role of macrophages and neutrophils.
abstract: Impaired immune function has been implicated in the declining health and higher incidence of cancer in the elderly. However, age-related changes to immunity are not completely understood. Neutrophils and macrophages represent the first line of defence yet their ability to phagocytose pathogens decrease with aging. Cytotoxic T lymphocytes are critical in eliminating tumors, but T cell function is also compromised with aging. T cell responses can be regulated by macrophages and may depend on the functional phenotype macrophages adopt in response to microenvironmental signals. This can range from pro-inflammatory, anti-tumorigenic M1 to anti-inflammatory, pro-tumorigenic M2 macrophages. Macrophages in healthy elderly adipose and hepatic tissue exhibit a more pro-inflammatory M1 phenotype compared to young hosts whilst immunosuppressive M2 macrophages increase in elderly lymphoid tissues, lung and muscle. These M2-like macrophages demonstrate altered responses to stimuli. Recent studies suggest that neutrophils also regulate T cell function and, like macrophages, neutrophil function is modulated with aging. It is possible that age-modified tissue-specific macrophages and neutrophils contribute to chronic low-grade inflammation that is associated with dysregulated macrophage-mediated immunosuppression, which together are responsible for development of multiple pathologies, including cancer. This review discusses recent advances in macrophage and neutrophil biology in healthy aging and cancer.
authors.affiliation: School of Biomedical Sciences, Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, 6102, Australia. Electronic address: connie.jackaman@curtin.edu.au.
authors.forename: Connie
authors.initials: C
authors.lastname: Jackaman
authors.affiliation: School of Biomedical Sciences, Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, 6102, Australia.
authors.forename: Federica
authors.initials: F
authors.lastname: Tomay
authors.affiliation: School of Biomedical Sciences, Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, 6102, Australia.
authors.forename: Lelinh
authors.initials: L
authors.lastname: Duong
authors.affiliation: School of Biomedical Sciences, Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, 6102, Australia.
authors.forename: Norbaini Bintu
authors.initials: NB
authors.lastname: Abdol Razak
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, 6009, Australia.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Pixley
authors.affiliation: School of Biomedical Sciences, Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, 6102, Australia.
authors.forename: Pat
authors.initials: P
authors.lastname: Metharom
authors.affiliation: School of Biomedical Sciences, Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, 6102, Australia.
authors.forename: Delia J
authors.initials: DJ
authors.lastname: Nelson
mesh_terms: D000375:Aging / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009765:Obesity / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators
keywords: Aging; Cancer; Macrophage; Neutrophil; Tumor microenvironment