Immunotherapy in older patients with cancer.

ABSTRACT

Ageing implicates a remodeling of our immune system, which is a consequence of the physiological senescence of our cells and tissues coupled with environmental factors and chronic antigen exposure. An immune system that senesces includes more differentiated cells with accumulation of highly differentiated CD4 and CD8 T cells. The pool of naive T cells decreases with the exponential thymic involution induced by age. Differentiated T cells have similar, if not higher, functional capacities but scarce studies are looking at the impact of senescence among specific T cells. After a stimulation, other immune cells (monocytes, dendritic cells and NK) are functionally altered during ageing. It is as if the immune system was more efficient at the basal level, but less efficient after a stimulation in the old compared to young people, likely due to less reserve. Concerning the clinical impact, older people are more prone to certain pathogens and their clinical manifestations differ from the younger people. Severe flu and VZV reactivation are more frequent with an altered cellular response to vaccination. Vaccination failure can have detrimental consequences in people presenting frailty criteria. Old people frailty is majored by their comorbidities and diseases like cancer. Thus, chemotherapies are employed with circumspection in older patients. The use of anti-PD-1/PD-L1 immunotherapies is therefore attractive, because of less side effects with a better response compared to chemotherapy. Old persons inclusion is lacking in current studies and clinical trials. Some subgroups or pooled analyses confirm the gain in response without increased toxicities in older patients but their inclusion criteria differ from the real-life practice. Specific studies focusing on this population are needed because of the increasing cancer incidence with age and the overall ageing of the population.