Abstract
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.
Highlights
Each year, ∼300,000 children are diagnosed with a form of cancer globally. (Steliarova-Foucher et al, 2017)
Many of the initial studies defining immunosenescence were performed in unique cohorts of centenarians, allowing the identification of immunosenescent cellular phenotypes/markers that enable successful aging (Effros et al, 1994; Fagnoni et al, 1996; Ostan et al, 2008)
Stemming from this work, several possible mechanisms were proposed to account for the development of immunosenescence, including 1) decrease in naïve T cells accompanied by expansion of memory T cell subsets with age; (Saule et al, 2006) 2) changes in myeloid cells, monocytes; (Hearps et al, 2012) 3) chronic low-grade inflammation (CLGI); (Fülöp et al, 2019) and 4) chronic infection with pathogens such as cytomegalovirus (CMV) (Olsson et al, 2000; Koch et al, 2007; Kallemeijn et al, 2017)
Summary
Each year, ∼300,000 children are diagnosed with a form of cancer globally. (Steliarova-Foucher et al, 2017). Each year, ∼300,000 children are diagnosed with a form of cancer globally. Cancer therapy has made immense progress in recent decades, increasing the 5 year survival rate to up to 85% in countries with advanced healthcare systems (Gatta et al, 2014; Howlader et al, 2020). With this great step forward, a significant problem has emerged: childhood cancer survivors (CCS) have a higher incidence of developing other, severe health conditions compared to their siblings (Armstrong et al, 2014), with up to 75% experiencing at least one late adverse effect and 40% suffering from at least one serious or life-threatening condition in early-mid adulthood
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