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: Connie Jackaman, Delia J Nelson
• Journal: Experimental gerontology (Exp Gerontol) Vol. 54 Pg. 53-7 (Jun 2014) ISSN: 1873-6815 [Electronic] England
• PMID: 24291067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents

Topics

• Aged
• Aging (immunology)
• Animals
• Antineoplastic Agents (therapeutic use)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Humans
• Immune Tolerance (physiology)
• Immunity, Innate (immunology)
• Macrophages (physiology)
• Myeloid Cells (physiology)
• Neoplasms (drug therapy, immunology)
• Neutrophils (physiology)
• T-Lymphocytes (physiology)
• Tumor Microenvironment (immunology)