ArticleJournal of cachexia, sarcopenia and muscle2025
Thymic Microenvironment Remodeling in Cancer Cachexia as a Determinant of Checkpoint Inhibitor Efficacy and Toxicity.
Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Sarcopenia modifies the survival benefit of triple therapy versus TACE alone in elderly patients with unresectable hepatocellular carcinoma: A multicenter retrospective cohort study.Scientific reports · 2026Article
- Stemness CD24 activation promotes hepatocellular carcinoma progressionWorld journal of gastroenterology · 2026Article
- Mechanism and intervention strategy of thymus atrophy in cancer immunotherapy.American journal of cancer research · 2026Review
- Cancer cachexia as an immunometabolic syndrome: targeting the immunometabolic interface with traditional Chinese Medicine monomers and formulas.Frontiers in immunology · 2026Review
- Radiographic evidence of thymic involution in hepatocellular carcinoma: a propensity score-matched study in viral cirrhosis.Frontiers in immunology · 2026Article
- Thymic regeneration and tumor immunotherapy.Frontiers in immunology · 2026Review
- Thymic Microenvironment Remodeling in Cancer Cachexia as a Determinant of Checkpoint Inhibitor Efficacy and Toxicity.Journal of cachexia, sarcopenia and muscle · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
backgroundThe discovery of immune checkpoints links autoimmunity and cancer, with thymus atrophy reportedly causing autoimmune multiorgan inflammation. The impact of cancer cachexia on thymic involution and its clinical significance remains unclear. This study aimed to investigate this effect and its association with immune checkpoint inhibitor (ICI) treatment.
methodsSingle-cell sequencing, immunofluorescence and flow cytometry analyses were conducted to explore changes in the thymus in orthotopic hepatocellular cancer (HCC) mice with cachexia. Patients with advanced and locally advanced cancers receiving anti-PD-1/L1 antibody treatment were followed up to investigate the relationship between the amount of serum autoantibodies and the efficacy of ICIs.
resultsSingle-cell sequencing in cachexic HCC mice revealed thymic fibroblast maturity disorders characterized by elevated immature medullary fibroblasts, impaired antigen processing functions, reduced interaction with single-positive thymocytes and decreased expression of tissue-restricted antigen-related genes. The thymus of mice with cancer cachexia exhibited degradation of the thymic medulla and decreased expression of LtβR, Mmp9 and Ccl19 in thymus medullary fibroblasts (mFbs). Single-cell TCR sequencing showed that inflammatory-related V/J TCR genes were highly used in expanded thymocyte clonotypes in cachexic HCC mice, suggesting impaired T cell negative selection. Results from coculture and cell transfer assays suggest that cancer cachexic CD45
conclusionsCancer cachexia disrupts mFbs maturity, affecting T cell negative selection and expanding the TCR repertoire against tissue-restricted antigens. This might mediate the adverse and favourable effects of ICIs as anticancer treatments.
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