Spermidine - an old molecule with a new age-defying immune function

Kenji Chamoto; Baihao Zhang; Masaki Tajima; Tasuku Honjo; Sidonia Fagarasan

doi:10.1016/j.tcb.2023.08.002

Spermidine - an old molecule with a new age-defying immune function

Trends Cell Biol. 2023 Sep 16:S0962-8924(23)00166-6. doi: 10.1016/j.tcb.2023.08.002. Online ahead of print.

Authors

Kenji Chamoto¹, Baihao Zhang², Masaki Tajima³, Tasuku Honjo⁴, Sidonia Fagarasan⁵

Affiliations

¹ Department of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Immuno-Oncology PDT, Kyoto University Graduate School of Medicine, Kyoto, Japan.
² Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan; Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
³ Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁴ Department of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁵ Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan; Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: sidonia.fagarasan@riken.jp.

PMID: 37723019
DOI: 10.1016/j.tcb.2023.08.002

Abstract

Polyamines - putrescine, spermidine, and spermine - are widely distributed aliphatic compounds known to regulate important biological processes in prokaryotic and eukaryotic cells. Therefore, spermidine insufficiency is associated with various physio-pathological processes, such as aging and cancers. Recent advances in immuno-metabolism and immunotherapy shed new light on the role of spermidine in immune cell regulation and anticancer responses. Here, we review novel works demonstrating that spermidine is produced by collective metabolic pathways of gut bacteria, bacteria-host co-metabolism, and by the host cells, including activated immune cells. We highlight the effectiveness of spermidine in enhancing antitumor responses in aged animals otherwise nonresponsive to immune checkpoint therapy and propose that spermidine supplementation could be used to enhance the efficacy of anti-PD-1 treatment.

Keywords: antitumor immunity; collective metabolic pathways; fatty acid oxidation; immuno-metabolites; mitochondria; spermidine.

Publication types

Review