Effect of organism aging on the development of anti-PD-(L)1 therapy-associated adverse events

Immune checkpoint inhibitor (ICI)-mediated release of immune suppression involves the risk of (re)activating the immune responses to self-tissues, which are considered 'side effects' of this therapy, immune-related adverse events (irAEs). Although the incidence of certain types of irAEs appears to be considerably increased in older patients, the effect of chronological aging on irAE development and their causative immunological mechanism are unclear. This review summarizes the potential relevance of chronological and cellular aging, such as age-associated changes in T-cell functions and aged environmental factors, and inflamm-aging, in shaping irAE-inducing immune responses. Several immunological perspectives on aging may provide insights into the practical consideration of the toxicity risks of ICIs, particularly in elderly patients. These insights from patient specimens and pre-clinical animal models will help establishing mechanism-based management strategies, including stratification of irAE-prone patients, and broadening the patient population that benefits from cancer immunotherapy, even in a younger population.