Immunosenescence and cancer immunotherapy at old age: Basics

Abstract

Age is the single most important risk factor for cancer development. Of the many age-associated changes paralleling increased cancer incidence, those of the immune system may play a major role in waning defense against tumorigenesis. Thus, immunosenescence may contribute to the higher rate of occurrence of tumors in the elderly. However, exactly how these age-related changes in immunity translate to cancer development is not well defined and understood. With the dramatic recent successes of immunotherapy in some patients for some tumors, there is an increasing concern that immunosenescence may temper responses in older patients. Nonetheless, existing anecdotal data suggest that success rates and side effects of first-generation checkpoint blockade immunotherapy in elderly patients are similar to those in younger subjects. However, success rates are still low, with only a fraction of patients obtaining clinical benefit in most trials, and it cannot yet be excluded that age may play a role in the failure of some therapies in some patients. Thus, although there are no reasons to refuse the elderly these treatments, appropriate clinical trials and not just anecdotal evidence are required to explore this issue further.