Are macrophages, myeloid derived suppressor cells and neutrophils mediators of local suppression in healthy and cancerous tissues in aging hosts?

Our plain-English summary of Are macrophages, myeloid derived suppressor cells and neutrophils mediators of local suppression in healthy and cancerous tissues in aging hosts?, by C. Jackaman, D.J. Nelson (Experimental Gerontology, 2014).

The study

• Authors: C. Jackaman, D.J. Nelson
• Journal: Experimental Gerontology
• Published: 2014;54:53-7
• Type of article: Review
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

In plain English

This article was a review, not a new study. The authors discussed research on how aging affects innate immune cells (dendritic cells, macrophages, myeloid derived suppressor cells and neutrophils) and their interactions with T cells, focusing on lung carcinomas and mesothelioma. No asbestos exposure was studied. The introduction mentioned asbestos as causing malignant mesothelioma and described a 30 to 45 year latency before diagnosis. It also cited earlier research (Reid et al., 2007) reporting a lower mesothelioma risk in children exposed to asbestos than in adults. Much of the evidence came from the authors' own mouse experiments. In one 2013 study, elderly (17 to 24 month old) mice had a significant decrease in M1 and an increase in M2 macrophages in spleens and bone marrow compared with young (6 to 8 week old) mice. There, activating elderly-derived macrophages with agonist anti-CD40 antibody plus IL-2 restored some elderly-derived CD8+ T cell functions. Earlier work found that more than 40% of cells in mouse mesothelioma and lung carcinoma tumors were macrophages. The authors proposed that combining 'rejuvenation' immunotherapy with standard chemotherapy may offer an improved outcome for elderly cancer patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review (perspective article summarizing published literature and the authors' own earlier and unpublished work); no new study reported
• Who was studied: No study population; the review discussed research on innate immune cells and T cells in young versus elderly hosts (mostly mice, some human data), with a focus on lung carcinomas and mesothelioma
• Exposure: No asbestos exposure was studied; the review concerned aging and tumor-related effects on immune cells. Asbestos appeared only in the introduction: as the cause of malignant mesothelioma, in a 30 to 45 year latency between asbestos exposure and diagnosable mesothelioma, and in a cited earlier study (Reid et al., 2007) reporting that children exposed to asbestos had a lower risk of mesothelioma than adults.
• Main results:
  • The authors cited their earlier study (Jackaman et al., 2013): the proportion of macrophages in lymphoid organs increased in mice during aging. This was associated with a significant decrease in M1 and an increase in M2 macrophages in spleens and bone marrow of elderly (17 to 24 month old) relative to young (6 to 8 week old) mice.
  • Citing the same earlier study: macrophages from elderly, but not young, mice exposed to tumor conditioned media from murine mesothelioma and Lewis lung carcinoma cells produced IL-4 and high levels of TGF-beta.
  • Citing earlier work (Jackaman et al., 2009): more than 40% of cells in murine mesothelioma and lung carcinoma tumors were macrophages.
  • Citing earlier work (Jackaman et al., 2012) in mice: depletion of CD8+ cytotoxic T cells abolished cisplatin-induced tumor regression and reduced the effectiveness of gemcitabine.
  • Citing Jackaman et al., 2013: activating elderly-derived macrophages with an agonist anti-CD40 antibody plus IL-2 rescued secretion of IFN-gamma and perforin by elderly-derived CD8+ T cells.
• The authors' conclusion: The authors proposed that combining 'rejuvenation' immunotherapy with standard chemotherapy may offer an improved outcome for elderly cancer patients. They also proposed that mouse models can be representative of human cancers, including mesothelioma and lung cancer, if elderly mice are used.
• Limitations the authors state:
  • The authors stated that it is not known whether aging harms interactions among tissue immune cells, or whether developing tumors make this worse.
  • The authors stated that the effect of age-related and tumor-related immune dysfunction on the outcome of chemotherapy is unknown.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Carcinoma, Mesothelioma, Chemotherapy, Immunotherapy.

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