As life expectancy increases worldwide, more people are living to older ages, where chronic diseases are common but highly heterogeneous. Chronological age alone does not adequately reflect health status; frailty better identifies individuals at increased risk of adverse outcomes. Ageing and frailty are associated with immune senescence, affecting both innate and adaptive immunity, leading to higher susceptibility to infections and cancer.
This thesis investigates how age-related immune changes and frailty relate to disease outcomes in two major health challenges: COVID-19 and melanoma.
In hospitalized COVID-19 patients, frail patients exhibited lower CRP levels, while higher CRP levels predicted an increase in in-hospital mortality across all frailty groups. However, frailty did not modify the relationship between inflammatory markers and mortality, suggesting that the higher mortality risk in frail older patients is not solely explained by differences in...
Show moreAs life expectancy increases worldwide, more people are living to older ages, where chronic diseases are common but highly heterogeneous. Chronological age alone does not adequately reflect health status; frailty better identifies individuals at increased risk of adverse outcomes. Ageing and frailty are associated with immune senescence, affecting both innate and adaptive immunity, leading to higher susceptibility to infections and cancer.
This thesis investigates how age-related immune changes and frailty relate to disease outcomes in two major health challenges: COVID-19 and melanoma.
In hospitalized COVID-19 patients, frail patients exhibited lower CRP levels, while higher CRP levels predicted an increase in in-hospital mortality across all frailty groups. However, frailty did not modify the relationship between inflammatory markers and mortality, suggesting that the higher mortality risk in frail older patients is not solely explained by differences in inflammatory responses.
In older patients with metastatic melanoma treated with anti-PD-1 immune checkpoint inhibitors, ageing and frailty were associated with some changes in T cell subsets, but these differences were not linked to treatment response. Finally, we observed trends toward higher immune-related toxicity, hospitalization, and treatment discontinuation among frail patients with cancer, although these did not reach statistical significance. Frail patients also appeared less tolerant of even low-grade toxicity.
Show less
