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

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.

Keywords: accelerated aging; childhood cancer survivor; elderly; immunosenescence; late effects; low-grade inflammation; patient stratification.

FIGURE 1

The prevalence of age-associated complications in CCS and siblings/control population. Data marked ^# has a mean age of 26.6 years (range 18–48) for CCS and a mean age of 29.2 years (range 18–56) for siblings (Oeffinger et al., 2006); data marked * has a median age of 33.7 years (range 11–58) in CCS and a median age of 36 years (range 7–62) for siblings (Armstrong et al., 2013); data marked ^$ has a mean age of 33.6 years (range 18–50) for CCS and a mean age of 29 years (range 18–50) for the control population (Ness et al., 2013). Malignant neoplasm represents secondary neoplasms for CCS and primary neoplasms for siblings/control population. Abbreviation: CV, cardiovascular.

FIGURE 2

The surface markers implicated in the immunosenescence phenotype of designated cells. Abbreviations: KLRG-1, Killer cell lectin like receptor sub family G member 1; NK, natural killer cells.

FIGURE 3

Immunophenotype, comorbidities, CLGI, and senescence markers suggested for CCS patient stratification.; Abbreviations: CM, central memory; TEMRA, terminally differentiated effector memory T cells re-expressing CD45RA; CVD, cardiovascular disease; DM, diabetes mellitus; ED, endocrinal disease; PD, pulmonary disease.