The importance of the age factor in cancer vaccination at older age

Abstract

Cancer is an age-related disease, and with the graying of the society there is an increasing need to optimize cancer management and therapy to elderly patients. Vaccine therapy for cancer is less toxic than chemotherapy or radiation and could be, therefore, especially effective in older, more frail cancer patients. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to T cell unresponsiveness, a phenomenon also observed in cancer patients per se. Therefore, research is needed to establish whether age-specific tumor-immunological variables permit optimal use of cancer vaccines and therapy in the elderly. This review summarizes the current knowledge of T cell unresponsiveness in cancer patients and elderly, and the results of cancer vaccination in preclinical models at young and old age. Finally, new directions that may lead to effective cancer vaccination at older age will be proposed.

The impact of aging on cancer vaccination

“…In cancer patients cytotoxic T lymphocytes (CTL), recognizing tumor-associated antigens (TAA) in association with major histo-compatibility complex (MHC) molecules on the tumor cells through their T cell receptor, and expected to destroy tumor cells when exposed simultaneously to both TAA/self-MHC complexes and co-stimulatory molecules, are often found at the site of the tumor, but have evidently been unable to destroy the tumor cells [25]. Multiple possible causes have been described for this unresponsiveness of the CTL in cancer patients [for a review see 4].…”

Cancer Vaccines: Emphasis on Pediatric Cancers

“…There was also an increased production of IL-2 and interferon-gamma after restimulation of the T cells in vitro in the young but not the old mice. Some of that difference could be abrogated by the use of granulocyte macrophage colony stimulating factor at the time of priming of the immune response [19]. These studies and many others led to the general conclusion that elderly patients are not expected to respond as well as a younger patient population to cancer vaccines.…”

“…There are multiple proposed reasons for the decreased immune function associated with aging that include among others, defect of antigen presenting cells, a shift from type 1 to type 2 of Th cells [7,19], increase in the number of memory T cells [19], deficiencies in production of secondary antibody isotypes [20], aberrant regulation of tyrosine kinases associated with T cell receptors [19], changes in the expression of various cluster of differentiation (CD) populations [19], and decreased cytokine production, for example interleukin (IL) 2, 6, 1 [20]. In addition, new naïve T cells cannot be produced in adults in numbers comparable to children as the thymic function diminishes with age and the thymus fully atrophies by age 60 [18] In a study testing a vaccine composed of mammary tumor cells engineered to express IL-2, 90% of young mice were protected from tumor challenge compared to only 10% of old mice.…”

Aging and Cancer Vaccines

“…33 Multiple possible causes have been described for this unresponsiveness of the CTL in cancer patients (for a review see Gravekamp 6 ). This includes decreased expression of MHC, TAA, or co-stimulatory molecules by tumor cells, and immune suppression induced by the primary tumors.…”