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Review
. 2025 Jun:111:48-59.
doi: 10.1016/j.semcancer.2025.02.012. Epub 2025 Feb 26.

Immunosenescence in skeletal muscle: The role-play in cancer cachexia chessboard

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Free article
Review

Immunosenescence in skeletal muscle: The role-play in cancer cachexia chessboard

Matteo Giovarelli et al. Semin Cancer Biol. 2025 Jun.
Free article

Abstract

With the increase in life expectancy, age-related conditions and diseases have become a widespread and relevant social burden. Among these, immunosenescence and cancer cachexia play a significant often intertwined role. Immunosenescence is the progressive aging decline of both the innate and adaptive immune systems leading to increased infection susceptibility, poor vaccination efficacy, autoimmune disease, and malignancies. Cancer cachexia affects elderly patients with cancer causing severe weight loss, muscle wasting, inflammation, and reduced response to therapies. Whereas the connections between immunosenescence and cancer cachexia have been raising attention, the molecular mechanisms still need to be completely elucidated. This review aims at providing the current knowledge about the interplay between immunosenescence, skeletal muscle, and cancer cachexia, analyzing the molecular pathways known so far to be involved. Finally, we highlight potential therapeutic strategies suited for elderly population aimed to block immunosenescence and to preserve muscle mass in cachexia, also presenting the analysis of the current state-of-the-art of related clinical trials.

Keywords: Cancer cachexia; Immune system; Immunosenescence; Sarcopenia; Skeletal muscle.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no conflicts of interest.