Low‐grade chronic inflammation and immune alterations in childhood and adolescent cancer survivors: A contribution to accelerated aging?

Sulicka-Grodzicka, Joanna; Surdacki, Andrzej; Seweryn, Michał; Mikołajczyk, T.; Rewiuk, Krzysztof; Guzik, Tomasz J.; Grodzicki, Tomasz

doi:10.1002/cam4.3788

Cited by 17 publications

(16 citation statements)

References 43 publications

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“…Pediatric cancer survivors differ from age-related controls in terms of activation of the adaptive immune system, chronic, low-grade inflammation, as well as immune tolerance resulting from the synthesis of immunomodulators via the tryptophan-kynurenine metabolic pathway [ 127 ]. These changes resemble an aging phenotype observed in older populations [ 128 ] and are indicative of allostatic load [ 127 ]. Some research shows that pediatric cancer survivors have increased biological age relative to their chronological age, as indicated by shortened telomeres [ 104 , 105 ], epigenetic age acceleration [ 106 ] and biochemical and molecular markers such as inefficient oxidative phosphorylation, increased lipid peroxidation and decreased expression of metabolic proteins and those involved in mitochondrial biogenesis [ 107 ].…”

Section: Target Organ Activationmentioning

confidence: 83%

The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients

White

Caterini

McCann

et al. 2021

Cancers

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Stress is a ubiquitous experience that can be adaptive or maladaptive. Physiological stress regulation, or allostasis, can be disrupted at any point along the regulatory pathway resulting in adverse effects for the individual. Children with cancer exhibit significant changes to these pathways in line with stress dysregulation and long-term effects similar to those observed in other early-life stress populations, which are thought to be, in part, a result of cytotoxic cancer treatments. Children with cancer may have disruption to several steps in the stress-regulatory pathway including cognitive-affective function, neurological disruption to stress regulatory brain regions, altered adrenal and endocrine function, and disrupted tissue integrity, as well as lower engagement in positive coping behaviours such as physical activity and pro-social habits. To date, there has been minimal study of stress reactivity patterns in childhood illness populations. Nor has the role of stress regulation in long-term health and function been elucidated. We conclude that consideration of stress regulation in childhood cancer may be crucial in understanding and treating the disease.

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Section: Target Organ Activationmentioning

confidence: 83%

The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients

White

Caterini

McCann

et al. 2021

Cancers

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“…In particular, in childhood cancer survivors (CCS) a premature aging process is observed which induces the damage of vital organs and, consequently, the onset of chronic age-related diseases, such as osteoporosis, cardiovascular diseases, obesity, and infertility [4,[37][38][39][40]. This condition is named frailty and is subsequent to a low-grade systemic chronic inflammation, inflamm-aging, caused by chemo-and radiotherapy insults [35]. Anti-neoplastic therapies are responsible for inflammation and for an increase of senescent cells, DNA mutation, and oxygen reactive species (ROS) production [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Sulicka-Grodzicka et al evaluated factors discriminating CS from controls, comparing selected biomarkers and lymphocyte subpopulations. They demonstrated that survivors had higher levels of C-reactive protein (CRP) and a shift towards activated CD8+CD38+ T cells [ 35 ]. CD38 is an important marker that regulates activation and proliferation of human T lymphocytes.…”

Section: Inflamm-aging and Immune System Alterationsmentioning

confidence: 99%

“…Moreover, ROS/RNS stimulate the production of cytokines and adhesion molecules, and lymphocytes activation and proliferation [ 34 ]. The resulting condition of chronic low-grade systemic inflammation is named “inflamm-aging” [ 35 ]. Chronic inflammation shares several features of acute inflammation; however, it is persistent and of a low grade and induces responses that lead to tissue damage.…”

Section: Introductionmentioning

confidence: 99%

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Biological Aspects of Inflamm-Aging in Childhood Cancer Survivors

Paola

Pota

Argenziano

et al. 2021

Cancers

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Anti-cancer treatments improve survival in children with cancer. A total of 80% of children treated for childhood cancer achieve 5-year survival, becoming long-term survivors. However, they undergo several chronic late effects related to treatments. In childhood cancer survivors a chronic low-grade inflammation, known as inflamm-aging, is responsible for frailty, a condition characterized by vital organ failure and by premature aging processes. Inflamm-aging is closely related to chemotherapy and radiotherapy, which induce inflammation, accumulation of senescent cells, DNA mutations, and the production of reactive oxygen species. All these conditions are responsible for the onset of secondary diseases, such as osteoporosis, cardiovascular diseases, obesity, and infertility. Considering that the pathobiology of frailty among childhood cancer survivors is still unknown, investigations are needed to better understand frailty’s biological and molecular processes and to identify inflamm-aging key biomarkers in order to facilitate the screening of comorbidities and to clarify whether treatments, normally used to modulate inflamm-aging, may be beneficial. This review offers an overview of the possible biological mechanisms involved in the development of inflamm-aging, focusing our attention on immune system alteration, oxidative stress, cellular senescence, and therapeutic strategies.

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“…In the elderly, the activation status by only CD38 has been found to be decreased and by only HLA-DR increased in CD8 + T cells in elderly (Qin et al, 2016). Interestingly, terminally differentiated CD8 + T cells do not show a senescent phenotype in CCS like in elderly, while the central memory CD8 + and CD4 + T cells increase in both, CCS and elderly (Saule et al, 2006;Sulicka-Grodzicka et al, 2021).…”

Section: T Cellsmentioning

confidence: 96%

Immunosenescence in Childhood Cancer Survivors and in Elderly: A Comparison and Implication for Risk Stratification

et al. 2021

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The population of childhood cancer survivors (CCS) has grown rapidly in recent decades. Although cured of their original malignancy, these individuals are at increased risk of serious late effects, including age-associated complications. An impaired immune system has been linked to the emergence of these conditions in the elderly and CCS, likely due to senescent immune cell phenotypes accompanied by low-grade inflammation, which in the elderly is known as “inflammaging.” Whether these observations in the elderly and CCS are underpinned by similar mechanisms is unclear. If so, existing knowledge on immunosenescent phenotypes and inflammaging might potentially serve to benefit CCS. We summarize recent findings on the immune changes in CCS and the elderly, and highlight the similarities and identify areas for future research. Improving our understanding of the underlying mechanisms and immunosenescent markers of accelerated immune aging might help us to identify individuals at increased risk of serious health complications.

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Low‐grade chronic inflammation and immune alterations in childhood and adolescent cancer survivors: A contribution to accelerated aging?

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 17 publications

References 43 publications

The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients

The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients

Biological Aspects of Inflamm-Aging in Childhood Cancer Survivors

Immunosenescence in Childhood Cancer Survivors and in Elderly: A Comparison and Implication for Risk Stratification

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