Cancer immunotherapy and aging: Lessons from the mouse

Cancer is a disease of the elderly. Since demographic trends indicate that over the next decades the number of elderly people will increase substantially, strategies for cancer prevention and therapy need to be optimized to older patients. Immunotherapy, either through passive or active immunization is a highly targeted type of therapy that is potentially less toxic than chemotherapy or radiation and could, therefore, be especially effective in older, more frail cancer patients. In particular active immunization, i.e., employing patient's own immune system through vaccination, offers great promise since it can potentially keep cancer permanently at bay. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to diminished T-cell responses, a phenomenon also observed in cancer patients per se. To develop cancer vaccines that are effective at older age, the availability of preclinical models that can predict age effects on cancer vaccination is critically important. In this review, current knowledge of diminished T-cell responses in cancer patients and elderly, the results of cancer vaccination in preclinical models and human clinical trials and the impact of aging on immunotherapy will be discussed. Finally, experimental approaches will be proposed how to make cancer vaccines more effective at older age.