Impact of aging on cancer immunity and immunotherapy

The highest incidence of human cancers is seen in older people. Many parameters of immunity decrease in an ageassociated manner. These two statements are each uncontroversial. However, whether the reason for the increased frequency of cancers in the elderly is due to alterations of the immune system in the old is much more controversial. Considering that the concept of immunosurveillance against spontaneously arising tumors is itself still controversial, this is hardly surprising. However, the eYcacy of certain immunotherapy protocols in preclinical models and the much less reproducible but nonetheless occasionally highly eVective therapeutic successes achieved in humans encourages the belief that the immune system could be exploited to control tumor growth. The following “Symposium-in-Writing” was inspired by the belief that either active or adoptive immunotherapy or a combination of both will one day soon be entering standard clinical practice. Given that most studies, preclinical and clinical both, have most often been conducted in younger individuals, it is imperative to consider the eVect of age on outcome. Most obviously, the eVect of age on T cell response to vaccination will be of great importance, and also the eVect of the old host environment on the eYcacy of adoptively transferred immune eVectors needs consideration. Here, we have gathered a collection of papers which review the eVects of age on the host in terms of inXammatory status and immune responsiveness in the carcinogenic process. Salvioli et al. discuss possible reasons why centenarians are protected from cancer. This could be mediated by at least two diVerent mechanisms: low IGF-1-mediated responses and elevated production of anti-inXammatory mediators. A well-preserved p53-mediated response able to block tumorigenesis or to decrease cancer aggressiveness is also critical for cancer protection in centenarians. On the other hand, Caruso et al. discuss the eVect that inXammation has in promoting carcinogenesis. They conclude that only further knowledge of the regulation and function of inXammatory pathways in cancer will help to understand the mechanisms of tumor formation and progression, as well as to identify new targets for the reWnement of novel treatments, such as the pharmacogenomics approach. Other papers then discuss diVerent immunotherapy models where the age of the host and the age of the immune system have been speciWcally analyzed as variables aVecting the outcome of the treatment. There is a plethora of preclinical and clinical studies utilizing dendritic cell-based therapies for cancer. However, there are only a handful of studies evaluating the eVect of this type of therapy in the aging This editorial forms the introduction to the Symposium in Writing: Impact of Ageing on Cancer Immunity and Immunotherapy.