Immune cell aging is associated with compromised cancer immunosurveillance and reduced efficacy of some cancer immunotherapies. The ability to reverse immune cell aging to obtain more efficient anti-tumour reactive T cells would provide obvious benefits in clinical treatment. This could be achieved by acting on key fundamental cellular processes including metabolism and autophagy, which may subsequently influence T cell differentiation and effector functions. Polyamines, which can induce autophagy, have been shown both to enhance mitochondrial activity and have a direct effect on T cells. First by improving effector functions in CD8 T cells and, second, by regulating CD4 T cell differentiation. However, the exact interconnections between autophagy, mitochondrial activity and T-cell function remain to be elucidated. Most of the data on these fundamental processes have been collected from non-human systems, but fewer clinical data are available. We herein discuss the main evidence and speculate on the eventual benefit of affecting metabolism in an aged immune system to improve immunotherapy outcome.

Increasing life expectancy globally results in predictions that one in six people will be > 65 years of age by 2050. Because the occurrence of most cancers is strongly associated with older age, a significant increase in the number of older adults with cancer is to be expected. It is likely that increased cancer in older adults can be explained both by the greater duration of exposure to external factors such as ultraviolet radiation, alcohol, smoking and pollution (hence modifiable by non-medical means) as well as intrinsic factors (such as metabolic stress and reactive oxygen species). These insults contribute to DNA damage and mutation that can lead to carcinogenesis if not counteracted by the appropriate repair mechanisms, or other protective strategies. Tissues from cancer-free individuals frequently contain mutations commonly observed in cancer, but these cells remain dormant until some endogenous or exogenous events promote carcinogenesis. In ageing individuals, less efficient surveillance and immune responses against cancer may represent one such event, as well as the chronic low level inflammation commonly accompanying ageing. Additionally, because of comorbidities, older patients are less robust and it is more likely that polypharmacy interferes with cancer treatment. Despite all this awareness of the impact of ageing, most cancer research, both clinical and preclinical, fails to fully consider age-associated differences in cancer occurrence and treatment, and there are very few journals specifically dedicated to publishing explorations of these issues in either the basic research or clinical context. Hence, the time has come to establish a new journal dedicated to taking a holistic approach to all aspects of cancer in older individuals. We are therefore now welcoming papers that may shed light on these increasingly important issues.