title: Are macrophages, myeloid derived suppressor cells and neutrophils mediators of local suppression in healthy and cancerous tissues in aging hosts?
abstract: Most cancers emerge in elderly and immune-comprised hosts implying an important role for cancer immune surveillance. Here, we focus on the role of tissue-associated innate immune cells including antigen presenting cells (i.e. dendritic cells and macrophages), myeloid derived suppressor cells and neutrophils in healthy and cancer-bearing elderly hosts. Most cancers, including the cancers that we are interested in, i.e. lung carcinomas and mesothelioma, emerge in aging populations at a time when naïve T cell function is declining. CD8(+) cytotoxic T lymphocytes are critical anti-tumor effector cells, and their diminished function may contribute to cancer escape mechanisms in the elderly. Therefore, we compare the likely consequences of innate immune cell interactions with T cells in young versus elderly hosts. We examine data showing that elderly-derived innate cells are highly immunosuppressive and may provide a more tumorigenic milieu than their younger counterparts. Standard chemotherapy often only provides these patients a few extra months survival time. Recent evidence has shown that standard chemotherapy is not as effective in hosts devoid of T cells. Therefore, T cell dysfunction in the elderly may contribute to poor treatment outcomes. However, there is also evidence that T cell immunity can be rejuvenated via activated dendritic cells and/or macrophages. Combining 'rejuvenation' immunotherapy with standard chemotherapy may offer an improved outcome for elderly cancer patients. We explore this potential herein.
authors.affiliation: Immunology and Cancer Group, School of Biomedical Sciences, Curtin University, Perth, Western Australia 6102, Australia; School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Perth, Western Australia 6102, Australia. Electronic address: Connie.Jackaman@curtin.edu.au.
authors.forename: Connie
authors.initials: C
authors.lastname: Jackaman
authors.affiliation: Immunology and Cancer Group, School of Biomedical Sciences, Curtin University, Perth, Western Australia 6102, Australia; School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Perth, Western Australia 6102, Australia. Electronic address: Delia.Nelson@curtin.edu.au.
authors.forename: Delia J
authors.initials: DJ
authors.lastname: Nelson
mesh_terms: D000368:Aged; D000375:Aging / Q000276:immunology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007113:Immunity, Innate / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D022423:Myeloid Cells / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D009504:Neutrophils / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents
keywords: Aging; Cancer; Chemotherapy; Immunotherapy; Macrophage; Myeloid-derived suppressor cell; Neutrophil