The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity

Sidharth S. Jain; Giselle Burton Sojo; Harry Sun; Benjamin N. Friedland; Megan E. McNamara; Marcel O. Schmidt; Anton Wellstein

doi:10.20944/preprints202405.2008.v1

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preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202405.2008.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity

Sidharth S. Jain

Giselle Burton Sojo

Harry Sun

Benjamin N. Friedland

Megan E. McNamara

Marcel O. Schmidt

Anton Wellstein

Version 1 : Received: 29 May 2024 / Approved: 30 May 2024 / Online: 30 May 2024 (10:59:51 CEST)
Version 2 : Received: 6 June 2024 / Approved: 7 June 2024 / Online: 10 June 2024 (04:21:20 CEST)

A peer-reviewed article of this Preprint also exists.

Jain, S.S.; Burton Sojo, G.; Sun, H.; Friedland, B.N.; McNamara, M.E.; Schmidt, M.O.; Wellstein, A. The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity. Int. J. Mol. Sci. 2024, 25, 7013. Jain, S.S.; Burton Sojo, G.; Sun, H.; Friedland, B.N.; McNamara, M.E.; Schmidt, M.O.; Wellstein, A. The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity. Int. J. Mol. Sci. 2024, 25, 7013.

Abstract

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role, and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

Keywords

immune checkpoint inhibitor; aging; cellular senescence

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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