Can Modulation of Autophagy Reinvigorate T cells in the Elderly?

Else Marit Inderberg; Sébastien Wälchli

doi:10.37155/2972-4759-2023-01-01-6

Authors

Else Marit Inderberg Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, 0379 Oslo, Norway.
Sébastien Wälchli Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, 0379 Oslo, Norway.

DOI:

https://doi.org/10.37155/2972-4759-2023-01-01-6

Keywords:

aging, immune cells, immunotherapy, metabolism, autophagy

Abstract

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.

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