Caloric restriction maintains OX40 agonist-mediated tumor immunity and CD4 T cell priming during aging

Farazi, Michelle; Nguyen, Justine; Goldufsky, Josef W.; Linnane, Stephanie; Lukaesko, Lisa; Weinberg, Andrew D.; Ruby, Carl E.

doi:10.1007/s00262-014-1542-y

Cited by 31 publications

(20 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on our gene expression data, CR-induced effects in the colon seemed to be dominated by alterations in immune-and metabolism-related processes. Our findings are consistent with various studies showing that CR affected markers of immune function or reduced expression of inflammatory genes in different tissues and model species [54,56,57]. The imbalance between pro-and anti-inflammatory stimuli and subsequent manifestation of chronic, low-grade inflammation during aging are well-known for their involvement in age-related diseases [9].…”

Section: Discussionsupporting

confidence: 92%

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Kok

Lugt

Lute

et al. 2018

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

Diminished colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an effective strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here, we report the effects of lifelong CR on indicators of colonic health in aging C57Bl/6J mice. Compared to an ad libitum control and moderate-fat diet, 30% energy reduction was associated with attenuated immune- and inflammation-related gene expression in the colon. Furthermore, expression of genes involved in lipid metabolism was higher upon CR, which may point towards efficient regulation of energy metabolism. The relative abundance of bacteria considered beneficial to colonic health, such as Bifidobacterium and Lactobacillus, increased in the mice exposed to CR for 28 months as compared to the other diet groups. We found lower plasma levels of interleukin-6 and lower levels of various metabolites, among which are bile acids, in the colonic luminal content of CR-exposed mice as compared to the other diet groups. Switching from CR to an ad libitum moderate-fat diet at old age (24 months) revealed remarkable phenotypic plasticity in terms of gene expression, microbiota composition and metabolite levels, although expression of a subset of genes remained CR-associated. This study demonstrated in a comprehensive way that CR affects indicators of colonic health in aging mice. Our findings provide unique leads for further studies that need to address optimal and feasible strategies for prolonged energy deprivation, which may contribute to healthy aging.

show abstract

Section: Discussionsupporting

confidence: 92%

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Kok

Lugt

Lute

et al. 2018

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

show abstract

“…When used during 6-8 months, caloric restriction improved aCD40 treatment responses in models of sarcoma and breast cancer when mice were aged 12 months. Tumour antigenspecific CD4 1 but not CD8 1 T cell priming was similar to young controls [96]. Certain types of caloric restriction are tolerable in aged patients, and in young subjects can improve anti-tumour immunity [97].…”

Section: Caloric Restrictionmentioning

confidence: 86%

Considerations for successful cancer immunotherapy in aged hosts

Hurez

Padrón

Svatek

et al. 2016

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Immunotherapy is now experiencing unprecedented successes in treating various cancers based on new understandings of cancer immunopathogenesis. Nonetheless, although ageing is the biggest risk factor for cancer, the majority of cancer immunotherapy preclinical studies are conducted in young hosts. This review will explore age‐related changes in immunity as they relate to cancer immune surveillance, immunopathogenesis and responses to immunotherapy. Although it is recognized that declining T cell function with age poses a great challenge to developing effective age‐related cancer immunotherapies, examples of successful approaches to overcome this hurdle have been developed. Further, it is now recognized that immune functions do not simply decline with age, but rather change in ways than can be detrimental. For example, with age, specific immune cell populations with detrimental functions can become predominant (such as cells producing proinflammatory cytokines), suppressive cells can become more numerous or more suppressive (such as myeloid‐derived suppressor cells), drugs can affect aged immune cells distinctly and the aged microenvironment is becoming recognized as a significant barrier to address. Key developments in these and other areas will be surveyed as they relate to cancer immunotherapy in aged hosts, and areas in need of more study will be assessed with some speculations for the future. We propose the term ‘age‐related immune dysfunction’ (ARID) as best representative of age‐associated changes in immunity.

show abstract

“…Finally, exploring the effects of caloric restriction and gut microbiota on immunosenescence is another recent exciting area of discovery. Interestingly, in some preclinical models of sarcoma and breast cancer, caloric restriction preserved the efficacy of the CD4+ T-cells priming process in old mice [41]. Although the actual mechanism by which caloric restriction exerts beneficial effects on the immune system during aging is widely unknown, it likely involves metabolic changes, oxidative stress regulation, neuroendocrine homeostasis [42] and modulation of gut microbiota [43].…”

Section: Immunosenescence T Cell Senescence and Cancermentioning

confidence: 99%

Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: Does age really matter?

Ferrara

Mezquita

Auclin

et al. 2017

Cancer Treatment Reviews

129

106

View full text Add to dashboard Cite

Immunotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer (NSCLC), extending overall survival, with a favorable safety profile. However, there is still a gap of knowledge about the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. Data from randomized clinical trials testing ICIs are conflicting and often lack adequate statistical power. Although two large meta-analyses suggested an absence of a significant survival benefit in patients older than 75years, expanded access programs and retrospective cohort studies of ICIs in the real-life setting, showed comparable survival outcomes and safety profiles between older and younger patients. In this complex scenario, a further unresolved issue is the potential correlation between older age and immunotherapy primary resistance, a phenomenon probably linked to the continuous and progressive remodeling of immune functions with ageing, known as immunosenescence. Defining the role of ICIs in elderly NSCLC patients and exploring the molecular mechanisms underlying a possible lack of benefit or even accelerated tumor growth during immunotherapy are two major challenges for future research in this field of cancer treatment. In this review, we describe the major hallmarks of immunosenescence and we summarize the existing clinical data of ICIs in elderly NSCLC patients.

show abstract

Caloric restriction maintains OX40 agonist-mediated tumor immunity and CD4 T cell priming during aging

Cited by 31 publications

References 44 publications

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Considerations for successful cancer immunotherapy in aged hosts

Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: Does age really matter?

Contact Info

Product

Resources

About