The immune system and cancer

The interrelationship of immune response, old age and high incidence of cancer

In recent years several factors have been associated with the development of human cancers, including smoking, dietary factors, infectious agents (viruses and bacteria), chemicals, radiation and hereditary factors (see Chapter 2). The treatment of normal cells with these factors results in the mutation of a wide range of genes such as tumour suppressor genes or genes coding for growth factor, growth factor receptors, and motility and invasion factors. Such mutation can in turn result in malignant transformation of normal cells via the expression or release of either abnormal products or a high level of normal products (Hanahan and Weinberg, 2000).

As the incidence of cancer increases rapidly in old age, ageing is another important factor associated with human cancers. Around 65% of all cancers are diagnosed in people over the age of 65. Although the increasing accumulation of mutations in genes with time can be one factor that contributes to the high incidence of cancers in old age, recent evidence suggests that malfunction of the immune system may also contribute to the high incidence of cancers in elderly people (Burns and Leventhal, 2000; Ginaldi et al., 2001; Effros, 2003), e.g. it is well established that with increasing age there is deterioration of the immune response (i.e. immunosenescence) which results in increased susceptibility to infection, insufficient responses to vaccines and a high level of autoimmune disorders (Lords et al., 2001; Stacy et al.,

2002). In particular, one of the common alterations in old age is a decline in T-cell-mediated immune responses. The decline in CMI with age is a multifactorial phenomenon and could be caused by: (1) a decrease in the population of naive (resting) T lymphocytes with a concomitant increase in the population of antigen-specific memory T cells (i.e. exhaustion of immune resources); (2) the poor proliferative response of T cells to mitogens; and (3) a decrease in the expression of the co-stimulatory molecule (e.g. CD28) on T cells, together with an increase in the expression of the inhibitory molecule on CD4+ Th cells (Franceschi et al., 2000; Appay and Rowland-Jones, 2002; Effros,

2003). Although there is no significant change in the AMI responses and the innate immune response is largely unchanged or even upregu-lated in old age, a decline in the T-cell-mediated immune response, such as that mediated by CD4- Th cells (see Figure 7.2), can reduce the overall immune response against cancer cells and therefore contribute to the high incidence of cancer in older people (Lords et al., 2001; Chen et al., 2002).

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