Controversies and consensus on immune function and long-term health risks following adult thymectomy: a comprehensive review of molecular mechanisms and real-world evidence
Abstract
ObjectiveTo evaluate the long-term immunological, oncological, and clinical consequences of adult thymectomy by synthesizing recent basic, translational, and real-world clinical evidence.BackgroundHistorical surgical paradigms regarded the post-pubertal adult thymus as an immunologically redundant, fatty involuted organ, justifying routine “incidental” resection during cardiac procedures. A high-profile 2023 cohort study in The New England Journal of Medicine (NEJM) challenged this concept, reporting that adult thymectomy significantly increased 5-year all-cause mortality and cancer risk. Subsequent population-level studies (US SEER/NCDB, French PMSI) and deep-learning imaging cohorts have sparked debate, offering both corroborating and conflicting insights into adult thymic function.Methods and synthesisThis review synthesizes cellular mechanisms (TREC dynamics, TCR repertoire contraction, senescence-associated T cells, Treg lineage stability) and endocrine factors (thymulin-mediated myeloid regulation) with clinical data stratified by age at surgery, indication, resection extent, and follow-up duration.ConclusionsThe adult thymus remains functionally active, exporting naïve T cells and humoral immunomodulators like thymulin that maintain peripheral immune tolerance and restrain inflammaging. Clinical evaluation must differentiate between incidental resection (which induces avoidable iatrogenic immunosenescence) and therapeutic resection (e.g., for thymic epithelial tumors or myasthenia gravis), where removing a diseased, immunosuppressive microenvironment can reduce secondary cancer risk. Partial thymectomy (PT) is emerging as an option to preserve immunocompetence when oncologically feasible.
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BibTeX
@article{zhao2026controversies,
title = {{Controversies and consensus on immune function and long-term health risks following adult thymectomy: a comprehensive review of molecular mechanisms and real-world evidence}},
author = {Pile Zhao and Xiumei Li and Xueqin Wang and Tongzhen Xu and Hengxiao Lu},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1903197},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1903197},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Controversies and consensus on immune function and long-term health risks following adult thymectomy: a comprehensive review of molecular mechanisms and real-world evidence
AU - Pile Zhao
AU - Xiumei Li
AU - Xueqin Wang
AU - Tongzhen Xu
AU - Hengxiao Lu
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1903197
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1903197
AB - ObjectiveTo evaluate the long-term immunological, oncological, and clinical consequences of adult thymectomy by synthesizing recent basic, translational, and real-world clinical evidence.BackgroundHistorical surgical paradigms regarded the post-pubertal adult thymus as an immunologically redundant, fatty involuted organ, justifying routine “incidental” resection during cardiac procedures. A high-profile 2023 cohort study in The New England Journal of Medicine (NEJM) challenged this concept, reporting that adult thymectomy significantly increased 5-year all-cause mortality and cancer risk. Subsequent population-level studies (US SEER/NCDB, French PMSI) and deep-learning imaging cohorts have sparked debate, offering both corroborating and conflicting insights into adult thymic function.Methods and synthesisThis review synthesizes cellular mechanisms (TREC dynamics, TCR repertoire contraction, senescence-associated T cells, Treg lineage stability) and endocrine factors (thymulin-mediated myeloid regulation) with clinical data stratified by age at surgery, indication, resection extent, and follow-up duration.ConclusionsThe adult thymus remains functionally active, exporting naïve T cells and humoral immunomodulators like thymulin that maintain peripheral immune tolerance and restrain inflammaging. Clinical evaluation must differentiate between incidental resection (which induces avoidable iatrogenic immunosenescence) and therapeutic resection (e.g., for thymic epithelial tumors or myasthenia gravis), where removing a diseased, immunosuppressive microenvironment can reduce secondary cancer risk. Partial thymectomy (PT) is emerging as an option to preserve immunocompetence when oncologically feasible.
SN - 1664-3224
ER -