Immune System Aging and Risk of Lymphoma

Cancer is an age-related condition in large part because the immune system declines with age. One of the many important tasks undertaken by the immune system is suppression of cancer. This is achieved by destroying cancerous and potentially cancerous cells quickly, before they can establish a tumor that will go on to subvert the immune system's normal responses to errant cells. This process of cancer eradication (and tumor development when eradication fails) is enormously complex in detail, but straightforward enough to understand at the high level. How does this interaction between aging, the immune system, and cancer risk work in practice when we are talking about a cancer of the immune system, however? The evidence suggests that persistent viral infection plays a larger direct role here than is the case in most other forms of cancer, which is intriguing given that these viral infections are also likely a major cause of adaptive immune system decline with age.

Immunosenescence is a peculiar remodeling of the immune system, caused by aging, associated with a wide variety of alterations of immune functions. It is has been implicated in pathophysiology of dementia, frailty, cardiovascular diseases, and it is the cause of increased susceptibility to infectious disease, autoimmunity, and cancer. Indeed, about 55% of tumors affect subjects who are over 65 years of age. It is well known that both the innate and the adaptive immune system protect the host against carcinogenesis by a process called "immunosurveillance". By means of this process, the immune cells identify and eliminate cancerous cells before a tumor develops.

The current available data focuses on B cell Non Hodgkin Lymphomas (NHL), which represent more than 90% of lymphoid neoplasms worldwide. Between lymphoma and aging, a complex interplay can be described. B cell NHLs develop by a multistep process closely related to normal B cell counterpart that can be favored with aging. As with all other cancer types, chronological ageing is associated with the accumulation of DNA damage particularly in stem cells. Also, epigenetic abnormalities that have a role in lymphoma and leukemia development can accumulate with aging.

In addition to abnormal genetic events, also age-related impairment in cancer protection is expected to promote B cell lymphomagenesis. The phenotype called "immunosenescence" is associated with a complex dysfunction that increases sensitivity to infections. Chronic infection with Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) in the elderly caused by restricted T cell response can alter the B cell immune repertoire, leading to infection-linked diseases as well as some types of lymphoma. Also, a causal relationship between Hepatitis C Virus (HCV) and NHL has been demonstrated and the most plausible molecular mechanism is lymphoma development by continuous antigenic stimulation.



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