Aging, Immunosenescence, and Cancer

Cancer is one of the most devastating diseases and occurs with higher frequency as we age. Indeed, one of the most important risk factors for most solid cancers is age. It is very difficult to define what links aging to cancer, considering the existence of multiple different cancers, the time needed for their development, and the multi-hit theory of carcinogenesis. Recently, eight hallmarks of cancer have been identified: these include having the ability to sustain proliferative signaling, evade growth suppressors, resist cell death, enable replicative immortality, induce angiogenesis, activate invasion and metastasis, reprogram energy metabolism, and escape the immune response. The immune system seems to play a crucial role in the control of cancer development and progression through its ability to mount an appropriate response, but it also favors cancer development by participating in the development of chronic inflammation. The apparent disequilibrium between retaining a relatively reactive innate immune response and developing a severely altered adaptive immune response with aging leads to the low-grade inflammatory status commonly observed in the elderly, termed inflammaging . Although the cause of this increased basal inflammatory state is certainly multifactorial, it is likely that one of the most important causes is chronic antigenic stimulation. Thus, in this chapter we will review the role of age-related dysregulated immunity in tumorigenesis.