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MULTIPLE MYELOMA, GAMMOPATHIES

Immune senescence in multiple myeloma—a role for mitochondrial dysfunction?

Leukemia volume 36, pages 2368–2373 (2022)Cite this article

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Abstract

Age-related immune dysfunction is primarily mediated by immunosenescence which results in ineffective clearance of infective pathogens, poor vaccine responses and increased susceptibility to multi-morbidities. Immunosenescence-related immunometabolic abnormalities are associated with accelerated aging, an inflammatory immune response (inflammaging) and ultimately frailty syndromes. In addition, several conditions can accelerate the development of immunosenescence, including cancer. This is a bi-directional interaction since inflammaging may create a permissive environment for tumour development. Multiple myeloma (MM) is a mature B-cell malignancy that presents in the older population. MM exemplifies the interaction of age- (Host Response Biology; HRB) and disease-related immunological dysfunction, contributing to the development of a frailty syndrome which impairs the therapeutic impact of recent advances in treatment strategies. Understanding the mechanisms by which accelerated immunological aging is induced and the ways in which a tumour such as MM influences this process is key to overcoming therapeutic barriers. A link between cellular mitochondrial dysfunction and the acquisition of an abnormal immune phenotype has recently been described and has widespread physiological consequence beyond the impact on the immune system. Here we outline our current understanding of normal immune aging, describe the mechanism of immunometabolic dysfunction in accelerating this process, and propose the role these processes are playing in the pathogenesis of MM.

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Fig. 1: Malignant plasma cells can influence T cell mitochondrial function via both direct and indirect mechanisms.

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Acknowledgements

This work was supported by the National Institute for Health Research (NIHR) infrastructure at Leeds, UK. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

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  1. Department of Haematology, Leeds Cancer Centre, Leeds Teaching Hospitals Trust, Leeds, UK

    Frances Seymour, Jonathan Carmichael, Christopher Parrish & Gordon Cook

  2. NIHR (Leeds) Medtech & In vitro Diagnostic Cooperative, Leeds, UK

    Jonathan Carmichael & Gordon Cook

  3. Experimental Haematology, Leeds Institute of Medical Research, University of Leeds UK, Leeds, UK

    Claire Taylor

  4. Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trial Research, University of Leeds UK, Leeds, UK

    Christopher Parrish & Gordon Cook

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Seymour, F., Carmichael, J., Taylor, C. et al. Immune senescence in multiple myeloma—a role for mitochondrial dysfunction?. Leukemia 36, 2368–2373 (2022). https://doi.org/10.1038/s41375-022-01653-7

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