ImmuneLENS characterizes systemic immune dysregulation in aging and cancer

TRACERx Consortium; Genomics England Consortium

doi:10.1038/s41588-025-02086-5

ImmuneLENS characterizes systemic immune dysregulation in aging and cancer

TRACERx Consortium, Genomics England Consortium

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower than in healthy individuals. Low circulating B cell fraction was linked to increased cancer incidence. Finally, circulating T cell abundance was more prognostic of 5-year cancer survival than infiltrating T cells.

Original language	English
Article number	305
Journal	Nature Genetics
Volume	57
Issue	3
Pages (from-to)	694-705
Number of pages	12
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-025-02086-5
Publication status	Published - Mar 2025

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@article{13299823e5314c80b08fd00524161dd4,

title = "ImmuneLENS characterizes systemic immune dysregulation in aging and cancer",

abstract = "Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower than in healthy individuals. Low circulating B cell fraction was linked to increased cancer incidence. Finally, circulating T cell abundance was more prognostic of 5-year cancer survival than infiltrating T cells.",

author = "Robert Bentham and Jones, {Thomas P.} and Black, {James R.M.} and Carlos Martinez-Ruiz and Michelle Dietzen and Maria Litovchenko and Kerstin Thol and Watkins, {Thomas B.K.} and Chris Bailey and Oriol Pich and Zhihui Zhang and {Van Loo}, Peter and Mathew Thomas and Jennifer Whiteley and Nikos Kostoulas and Rocco Bilancia and Mo Asif and Alan Kirk and {Le Quesne}, John and Craig Dick and Andrew Kidd and Blyth, {Kevin G.} and Peter Russell and Lily Robinson and Shackcloth, {Michael J.} and Sarah Danson and Madeleine Hewish and Chiara Proli and Pratibha Shah and Nadia Fernandes and Sarah Booth and Mpho Malima and Daniel Kaniu and Buderi, {Silviu I.} and Sofina Begum and Hema Chavan and Anand Devaraj and Lyn Ambrose and Harshil Bhayani and Hilgardt Raubenheimer and Alexandra Rice and Simon Jordan and {De Sousa}, Paulo and Nicholson, {Andrew G.} and Eric Lim and Judith Cave and Aiman Alzetani and Patricia Georg and Serena Chee and Birkbak, {Nicolai J.} and {TRACERx Consortium} and {Genomics England Consortium}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = mar,

doi = "10.1038/s41588-025-02086-5",

language = "English",

volume = "57",

pages = "694--705",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

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TY - JOUR

T1 - ImmuneLENS characterizes systemic immune dysregulation in aging and cancer

AU - Bentham, Robert

AU - Jones, Thomas P.

AU - Black, James R.M.

AU - Martinez-Ruiz, Carlos

AU - Dietzen, Michelle

AU - Litovchenko, Maria

AU - Thol, Kerstin

AU - Watkins, Thomas B.K.

AU - Bailey, Chris

AU - Pich, Oriol

AU - Zhang, Zhihui

AU - Van Loo, Peter

AU - Thomas, Mathew

AU - Whiteley, Jennifer

AU - Kostoulas, Nikos

AU - Bilancia, Rocco

AU - Asif, Mo

AU - Kirk, Alan

AU - Le Quesne, John

AU - Dick, Craig

AU - Kidd, Andrew

AU - Blyth, Kevin G.

AU - Russell, Peter

AU - Robinson, Lily

AU - Shackcloth, Michael J.

AU - Danson, Sarah

AU - Hewish, Madeleine

AU - Proli, Chiara

AU - Shah, Pratibha

AU - Fernandes, Nadia

AU - Booth, Sarah

AU - Malima, Mpho

AU - Kaniu, Daniel

AU - Buderi, Silviu I.

AU - Begum, Sofina

AU - Chavan, Hema

AU - Devaraj, Anand

AU - Ambrose, Lyn

AU - Bhayani, Harshil

AU - Raubenheimer, Hilgardt

AU - Rice, Alexandra

AU - Jordan, Simon

AU - De Sousa, Paulo

AU - Nicholson, Andrew G.

AU - Lim, Eric

AU - Cave, Judith

AU - Alzetani, Aiman

AU - Georg, Patricia

AU - Chee, Serena

AU - Birkbak, Nicolai J.

AU - TRACERx Consortium

AU - Genomics England Consortium

PY - 2025/3

Y1 - 2025/3

N2 - Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower than in healthy individuals. Low circulating B cell fraction was linked to increased cancer incidence. Finally, circulating T cell abundance was more prognostic of 5-year cancer survival than infiltrating T cells.

AB - Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower than in healthy individuals. Low circulating B cell fraction was linked to increased cancer incidence. Finally, circulating T cell abundance was more prognostic of 5-year cancer survival than infiltrating T cells.

UR - http://www.scopus.com/inward/record.url?scp=85218225916&partnerID=8YFLogxK

U2 - 10.1038/s41588-025-02086-5

DO - 10.1038/s41588-025-02086-5

M3 - Journal article

C2 - 39966644

AN - SCOPUS:85218225916

SN - 1061-4036

VL - 57

SP - 694

EP - 705

JO - Nature Genetics

JF - Nature Genetics

IS - 3

M1 - 305

ER -

ImmuneLENS characterizes systemic immune dysregulation in aging and cancer

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