Quantifiable TCR repertoire changes in prediagnostic blood specimens among patients with high-grade ovarian cancer

Yu, Xuexin; Pan, Mingyao; Ye, Jianfeng; Hathaway, Cassandra A.; Tworoger, Shelley S.; Lea, Jayanthi; Li, Bo

doi:10.1016/j.xcrm.2024.101612

Cited by 2 publications

(2 citation statements)

References 74 publications

(99 reference statements)

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“…We first implemented Repertoire Functional Unit, or RFU, our recent computational method to analyze the TCR repertoire samples 21 . In brief, each TCR sequence was projected to a 500dimensional Euclidean space, with shorter distance between a pair of TCRs representing higher similarity.…”

Section: Robustly Age-associated Tcr Signatures In Multiple Human Coh...mentioning

confidence: 99%

“…Such an investigation is challenging given the vast diversity of the human TCR repertoire 20 , yet it holds the promise to uncover shared 'aging antigens' that could be targeted in the older population for improved immune protection 6 . In this work, we seek to address this challenge with our newly developed TCR analysis method, Repertoire Functional Unit (RFU) 21 , which dissects the hypervariable TCR repertoire into quantifiable segments, or RFUs, that can be compared across different individuals. We applied this approach to investigate a large number of repertoire samples deeply sequenced for the β chain complementarity determining region 3 (CDR3) of TCRs and systematically studied the age associations of individual RFUs.…”

Section: Introductionmentioning

confidence: 99%

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Quantifiable Blood TCR Repertoire Components Associated with Immune Aging

Hu,

Pan,

Reid

et al. 2024

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T cell senescence results in decayed adaptive immune protection in older individuals, with decreased or increased abundance of certain T cell phenotypic subpopulations. However, no study has linked aging to the dynamic changes of T cell clones. Through a newly develop computational framework, Repertoire Functional Units (RFU), we investigated over 6,500 TCR repertoire sequencing samples from multiple human cohorts. Our analysis identified age-associated RFUs repeatedly and consistently across different cohorts. Quantification of RFU decreases with aging revealed accelerated loss under immunosuppressive conditions. Systematic analysis of age-associated RFUs in clinical samples manifested a potential link between these RFUs and improved clinical outcomes during acute viral infections, such as lower ICU admission and reduced risk of developing complications. Finally, our investigation of bone-marrow transplantation patients indicated a secondary expansion of the age-associated clones upon receiving stem cells from younger donors. Together, our results suggest the existence of certain clones or a TCR clock that could reflect the immune functions in aging populations.

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Section: Robustly Age-associated Tcr Signatures In Multiple Human Coh...mentioning

confidence: 99%