ImmuneLENS characterizes systemic immune dysregulation in aging and cancer
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.
Authors
- Hugo J.W.L. Aerts (ORCID: https://orcid.org/0000-0002-2122-2003)
- Cristina Naceur‐Lombardelli (ORCID: https://orcid.org/0000-0002-7097-0307)
- Teresa Marafioti (ORCID: https://orcid.org/0000-0003-1223-6275)
- Clare E. Weeden (ORCID: https://orcid.org/0000-0002-1561-1416)
- Kristina Ibáñez (ORCID: https://orcid.org/0000-0002-7718-814X)
- Jack Davies Hodgkinson
- Paulo De Sousa (ORCID: https://orcid.org/0000-0003-3011-4116)
- Chris A. Odhams
- D. Kasperaviciute
- F. Boardman-Pretty (ORCID: https://orcid.org/0000-0001-8459-4739)
- Reena Khiroya
- Tamara Denner
- Claudia Lee (ORCID: https://orcid.org/0000-0003-1715-2265)
- Xiaoxi Pan (ORCID: https://orcid.org/0000-0002-6146-5771)
- Carolyn Tregidgo
- Mathew Carter
- M. Bleda
- Tim Hubbard (ORCID: https://orcid.org/0000-0002-1767-9318)
- Dimitris Polychronopoulos (ORCID: https://orcid.org/0000-0001-9427-3082)
- Seng Kuong Anakin Ung (ORCID: https://orcid.org/0009-0007-7231-0461)
- Pedro Furió‐Tarí
- Mickael Escudero (ORCID: https://orcid.org/0000-0002-1336-815X)
- Pratibha Shah
- Anna C. Need (ORCID: https://orcid.org/0000-0003-3955-8207)
- J. Pullinger (ORCID: https://orcid.org/0000-0001-9357-1184)
- Richard Stone (ORCID: https://orcid.org/0000-0001-8059-3800)
- Gary Royle (ORCID: https://orcid.org/0000-0002-8548-7684)
- Nirupa Murugaesu (ORCID: https://orcid.org/0000-0002-5005-7908)
- Damian Smedley (ORCID: https://orcid.org/0000-0002-5836-9850)
- R. E. Foulger
- Corentin Richard (ORCID: https://orcid.org/0000-0001-9732-0219)
- L. Lahnstein
- Robert Stephens (ORCID: https://orcid.org/0000-0002-7510-1143)
- S. A. Watters
- Sergio A. Quezada (ORCID: https://orcid.org/0000-0002-9763-1700)
- Aiman Alzetani (ORCID: https://orcid.org/0000-0002-3373-6714)
- William Hill (ORCID: https://orcid.org/0000-0002-9591-1389)
- Melis Kayikci (ORCID: https://orcid.org/0000-0002-0170-1939)
- K. Savage
- Jayant K. Rane (ORCID: https://orcid.org/0000-0002-9594-3938)
- Simone Zaccaria (ORCID: https://orcid.org/0000-0002-5265-7392)
- Wei-Ting Lu (ORCID: https://orcid.org/0000-0002-1405-4806)
- Nikos Kostoulas
- Roberto Salgado (ORCID: https://orcid.org/0000-0002-1110-3801)
- Neal Navani (ORCID: https://orcid.org/0000-0002-6412-7516)
- Charles Swanton (ORCID: https://orcid.org/0000-0002-4299-3018)
- Hilgardt Raubenheimer
- Takahiro Karasaki (ORCID: https://orcid.org/0000-0001-6863-2360)
- Maria Litovchenko (ORCID: https://orcid.org/0000-0003-1868-4933)
- Ekaterini Boleti
- Andrew J. Atkin (ORCID: https://orcid.org/0000-0002-3819-3448)
- Lovett Lawson (ORCID: https://orcid.org/0000-0001-9019-7537)
- Yutaka Naito (ORCID: https://orcid.org/0000-0001-6827-601X)
- Camilla Pilotti
- Rachel Scott (ORCID: https://orcid.org/0000-0001-5847-3378)
- Sophia Ward (ORCID: https://orcid.org/0000-0002-6777-5279)
- A. Devereau (ORCID: https://orcid.org/0000-0003-0356-1519)
- Colin R. Lindsay (ORCID: https://orcid.org/0000-0001-8167-5461)
- Allan Hackshaw (ORCID: https://orcid.org/0000-0002-5570-5070)
- Alexander James Procter
- Dina Halai
- T. Rahim
- Paulina Prymas
- Katey S.S. Enfield (ORCID: https://orcid.org/0000-0002-4551-6073)
- James R. Black (ORCID: https://orcid.org/0000-0001-5598-7752)
- Jonas Demeulemeester (ORCID: https://orcid.org/0000-0002-2660-2478)
- Rebecca Boyles (ORCID: https://orcid.org/0000-0003-0073-6854)
- Richard H. Scott (ORCID: https://orcid.org/0000-0002-9113-2978)
- Zoltán Szállási (ORCID: https://orcid.org/0000-0001-5395-7509)
- Nikki Totton (ORCID: https://orcid.org/0000-0002-1900-2773)
- Magdalena Zarowiecki (ORCID: https://orcid.org/0000-0001-6102-7731)
- Olivia Lucas (ORCID: https://orcid.org/0000-0001-8169-7767)
- Alexandra Rice (ORCID: https://orcid.org/0000-0002-0527-7960)
- C. R. Boustred (ORCID: https://orcid.org/0000-0001-7739-9302)
- Anshuman Chaturvedi (ORCID: https://orcid.org/0000-0003-1575-1176)
- Louise C. Daugherty (ORCID: https://orcid.org/0000-0003-4546-6667)
- Oriol Pich (ORCID: https://orcid.org/0000-0002-1956-1882)
- Jeanette Kittel (ORCID: https://orcid.org/0000-0002-8964-4640)
- Gareth A. Wilson (ORCID: https://orcid.org/0000-0002-5703-9710)
- Vittorio Barbè
- M. J. Welland (ORCID: https://orcid.org/0000-0002-7683-6213)
- Jacki Goldman (ORCID: https://orcid.org/0000-0002-2981-5022)
- K. Sawant
- Maise Al Bakir (ORCID: https://orcid.org/0000-0002-0846-8332)
- David R. Pearce (ORCID: https://orcid.org/0000-0001-8443-2924)
- Mathew Thomas (ORCID: https://orcid.org/0000-0003-4609-0833)
- Kwang Cheol Koh (ORCID: https://orcid.org/0000-0002-9146-450X)
- Mairead MacKenzie
- Greg Elgar (ORCID: https://orcid.org/0000-0001-7323-1596)
- Jérôme Nicod (ORCID: https://orcid.org/0000-0003-2459-3480)
- Andrew Kidd (ORCID: https://orcid.org/0000-0003-1691-4395)
- Lily Robinson
- Roberto Vendramin (ORCID: https://orcid.org/0000-0001-7191-4887)
- Hanyun Zhang (ORCID: https://orcid.org/0000-0002-4140-7881)
- Sarah Benafif (ORCID: https://orcid.org/0000-0003-1407-1697)
- Emma Nye (ORCID: https://orcid.org/0000-0001-9154-3526)
- Simon R. Thompson (ORCID: https://orcid.org/0000-0001-6966-5842)
- Sonya Hessey (ORCID: https://orcid.org/0000-0001-9856-424X)
- Crispin T. Hiley (ORCID: https://orcid.org/0000-0002-5869-0775)
- Alexander M. Frankell (ORCID: https://orcid.org/0000-0002-0341-7878)
- Krupa Thakkar
- Abigail Bunkum (ORCID: https://orcid.org/0000-0002-7753-9421)
- Anca Grapa
- Apostolos Nakas (ORCID: https://orcid.org/0000-0001-6993-1514)
- Katherine R. Smith (ORCID: https://orcid.org/0000-0002-0329-5938)
- Yien Ning Sophia Wong (ORCID: https://orcid.org/0000-0003-1903-6110)
- Francesco Fraioli (ORCID: https://orcid.org/0000-0003-0821-6327)
- Gary Middleton (ORCID: https://orcid.org/0000-0001-5695-3474)
- I. U. S. Leong
- Pablo Riesgo-Ferreiro (ORCID: https://orcid.org/0000-0003-2739-1315)
- Benny Chain (ORCID: https://orcid.org/0000-0002-7417-3970)
- Heather Cheyne
- Mary Falzon (ORCID: https://orcid.org/0009-0006-6210-4376)
- Seton Henderson
- Caroline Dive (ORCID: https://orcid.org/0000-0002-1726-8850)
- Felice Granato
- Loukas Moutsianas (ORCID: https://orcid.org/0000-0001-5453-345X)
- Katarzyna Witkowska (ORCID: https://orcid.org/0000-0002-4691-4743)
- Victoria J. Spanswick
- P. Arumugam
- Amrita Bajaj (ORCID: https://orcid.org/0000-0002-9251-2753)
- Michelle Leung (ORCID: https://orcid.org/0000-0001-9555-1080)
- Molly Scotland
- Miklós Dióssy (ORCID: https://orcid.org/0000-0003-0308-6615)
- Maria Zagorulya (ORCID: https://orcid.org/0000-0002-4478-5378)
- Emma Colliver (ORCID: https://orcid.org/0000-0002-1497-0740)
- Mina Ryten (ORCID: https://orcid.org/0000-0001-9520-6957)
- Khalid AbdulJabbar (ORCID: https://orcid.org/0000-0002-4411-4435)
- Philip Hobson (ORCID: https://orcid.org/0000-0001-5117-2994)
- Thomas P. Jones (ORCID: https://orcid.org/0000-0003-2748-0780)
- Clare Puttick (ORCID: https://orcid.org/0009-0006-3022-8737)
- Supreet Kaur Bola (ORCID: https://orcid.org/0000-0001-8558-8197)
- Jonathan Tugwood
- Sridhar Rathinam (ORCID: https://orcid.org/0000-0002-1065-0045)
- Rachel Rosenthal (ORCID: https://orcid.org/0000-0002-0900-8709)
- Leah Ensell
- J. M. Hackett
- E. Walsh
- Tom L. Kaufmann (ORCID: https://orcid.org/0000-0003-4374-1338)
- Georgia Stavrou (ORCID: https://orcid.org/0000-0002-8427-5233)
- Alexander Stuckey (ORCID: https://orcid.org/0000-0001-8636-737X)
- Thomas B.K. Watkins (ORCID: https://orcid.org/0000-0001-7414-737X)
- Yin Wu (ORCID: https://orcid.org/0000-0003-4080-3935)
- David Lawrence
- Cian Murphy (ORCID: https://orcid.org/0000-0003-1356-959X)
- Dhruva Biswas (ORCID: https://orcid.org/0000-0001-9141-5188)
- Michael Mueller (ORCID: https://orcid.org/0000-0002-2056-1185)
- Mihaela Angelova (ORCID: https://orcid.org/0000-0002-0495-9695)
- Yvonne Summers
- Mariam Jamal‐Hanjani (ORCID: https://orcid.org/0000-0003-1212-1259)
- Rija Zaidi (ORCID: https://orcid.org/0000-0002-2259-4319)
- Gerald Langman
- Eva Grönroos (ORCID: https://orcid.org/0000-0001-8303-5409)
- Sean D. Smith (ORCID: https://orcid.org/0000-0002-7796-4313)
- Dionysis Papadatos-Pastos
- Lucrezia Patruno (ORCID: https://orcid.org/0000-0002-3721-9984)
- James M. Wilson (ORCID: https://orcid.org/0000-0002-9630-3131)
- Zoe Ramsden
- Scott Wood (ORCID: https://orcid.org/0000-0003-4543-8850)
- Ieva Usaite (ORCID: https://orcid.org/0000-0001-6154-0447)
- L. J. Jones
- Sara Waplington
- Ellen M. McDonagh (ORCID: https://orcid.org/0000-0001-5806-6174)
- Angeliki Karamani
- Kerstin Thol (ORCID: https://orcid.org/0000-0002-4624-118X)
- Tom Fowler (ORCID: https://orcid.org/0000-0002-7258-2279)
- Paul Bishop
- John A. Hartley (ORCID: https://orcid.org/0000-0003-3737-9897)
- Selvaraju Veeriah (ORCID: https://orcid.org/0000-0002-1217-0387)
- Allan D. Kirk (ORCID: https://orcid.org/0000-0003-2004-5962)
- Nicholas McGranahan (ORCID: https://orcid.org/0000-0001-9537-4045)
- Elena Williams (ORCID: https://orcid.org/0000-0001-5765-6738)
- Mpho Malima
- John Le Quesne (ORCID: https://orcid.org/0000-0003-3552-7446)
- George Kassiotis (ORCID: https://orcid.org/0000-0002-8457-2633)
- Michael Shackcloth (ORCID: https://orcid.org/0000-0002-6494-9907)
- Ricky M. Thakrar (ORCID: https://orcid.org/0000-0001-9793-2223)
- Kristiana Grigoriadis (ORCID: https://orcid.org/0000-0002-8435-0176)
- Babu Naidu
- F. J. Lopez (ORCID: https://orcid.org/0000-0002-4097-6281)
- Aya Osman (ORCID: https://orcid.org/0000-0002-2048-5039)
- Angela Leek
- Despoina Karagianni (ORCID: https://orcid.org/0000-0002-8605-5808)
- C. Bailey (ORCID: https://orcid.org/0000-0002-9438-3879)
- Răzvan Sultana (ORCID: https://orcid.org/0000-0002-6563-6267)
- Sean Dulloo
- David Moore (ORCID: https://orcid.org/0000-0002-3748-0154)
- Fleur Monk
- Nnennaya Kanu (ORCID: https://orcid.org/0000-0001-7232-1952)
- Helen Brittain (ORCID: https://orcid.org/0000-0002-1582-0031)
- Antonia Toncheva
- S. E. A. Leigh (ORCID: https://orcid.org/0000-0003-3368-7059)
- Davide Patrini (ORCID: https://orcid.org/0000-0002-2492-799X)
- Madava Djearaman
- Angela Hamblin (ORCID: https://orcid.org/0000-0002-0183-5910)
- Samuel Gamble
- Sadegh Saghafinia (ORCID: https://orcid.org/0000-0001-5695-9825)
- Carlos Martínez‐Ruiz (ORCID: https://orcid.org/0000-0002-4817-0565)
- Juliette Novasio
- Maria Chiara Pisciella
- Elizabeth Keene
- Serena Chee (ORCID: https://orcid.org/0000-0001-7244-9876)
- Sam M. Janes (ORCID: https://orcid.org/0000-0002-6634-5939)
- M. J. Caulfield
- Gurdeep Matharu
- Nadia J. Fernandes (ORCID: https://orcid.org/0000-0003-4595-9939)
- Francisco Gimeno-Valiente (ORCID: https://orcid.org/0000-0003-0544-9459)
- Anna de Burca
- J. E. Holman
- G. C. Chan
- Jacqui Shaw (ORCID: https://orcid.org/0000-0003-4227-503X)
- Emilie Martinoni Hoogenboom
- António Paiva‐Correia (ORCID: https://orcid.org/0000-0001-8725-0202)
- Helen L. Lowe (ORCID: https://orcid.org/0000-0001-8630-378X)
- Angela Dwornik
- Junaid Choudhary
- Roland F. Schwarz (ORCID: https://orcid.org/0000-0001-9155-4268)
- R. Jackson
- Akshay Jatin Patel (ORCID: https://orcid.org/0000-0001-9170-8618)
- A. Sosinsky
- Michelle Dietzen (ORCID: https://orcid.org/0000-0002-6853-7563)
- Sarah Danson (ORCID: https://orcid.org/0000-0002-3593-2890)
- Sofina Begum (ORCID: https://orcid.org/0000-0001-7689-0087)
- Pat Gorman
- A. Sieghart (ORCID: https://orcid.org/0000-0001-5484-4346)
- Mohamad Tufail
- F. Maleady-Crowe
- Gillian Price
- J.F. Lester (ORCID: https://orcid.org/0000-0002-2311-070X)
- Harshil Bhayani
- Philip Crosbie (ORCID: https://orcid.org/0000-0001-8941-4813)
- Carla Castignani (ORCID: https://orcid.org/0000-0001-8689-9659)
- Silviu Buderi
- James W. Holding
- Ariana Huebner
- Kayalvizhi Selvaraju
- Rachel Leslie
- Stefan Boeing (ORCID: https://orcid.org/0000-0003-0495-5659)
- Rocco Bilancia
- Arjun Nair (ORCID: https://orcid.org/0000-0001-9270-3771)
- A. Siddiq
- Erik Sahai (ORCID: https://orcid.org/0000-0002-3932-5086)
- Kendadai Rammohan
- A. Rendon
- Zoltán Káplár
- Peter Van Loo (ORCID: https://orcid.org/0000-0003-0292-1949)
- Catarina Veiga (ORCID: https://orcid.org/0000-0002-0911-152X)
- Azmina Sodha-Ramdeen
- Martin Förster (ORCID: https://orcid.org/0000-0003-3876-7269)
- Imran Noorani (ORCID: https://orcid.org/0000-0003-4289-2345)
- Nicolai J. Birkbak (ORCID: https://orcid.org/0000-0003-1613-9587)
- Matthew Krebs (ORCID: https://orcid.org/0000-0001-7540-3064)
- Kerstin Haase (ORCID: https://orcid.org/0000-0002-0944-5618)
- Christine Patch (ORCID: https://orcid.org/0000-0002-4191-0663)
- Eric Lim (ORCID: https://orcid.org/0000-0002-9078-3226)
- Tracey Cruickshank
- Sharon Vanloo
- Bashair M. Mussa (ORCID: https://orcid.org/0000-0002-1554-6319)
- Shirley Richardson
- Chiara Proli
- Kunal Bhakhri
- Jeffrey B. Mason (ORCID: https://orcid.org/0000-0003-2459-1186)
- Amy S. Walker (ORCID: https://orcid.org/0000-0003-0140-0586)
- Wing Kin Liu
- Elaine Borg (ORCID: https://orcid.org/0009-0000-6250-9695)
- Madeleine Hewish
- Paul Ashford (ORCID: https://orcid.org/0000-0003-4079-0257)
- Arianna Tucci (ORCID: https://orcid.org/0000-0001-5644-0070)
- Daniel Kaniu
- Emma L. Baple (ORCID: https://orcid.org/0000-0002-6637-3411)
- Charles‐Antoine Collins‐Fekete (ORCID: https://orcid.org/0000-0003-2464-8795)
- Fiona Helen Blackhall (ORCID: https://orcid.org/0000-0001-8716-3395)
- James L. Reading (ORCID: https://orcid.org/0000-0001-5381-978X)
- Andrew G. Nicholson (ORCID: https://orcid.org/0000-0003-3257-102X)
- Jennifer Whiteley
- Helen Shackleford
- Gerasimos-Theodoros Mastrokalos
- Zhihui Zhang (ORCID: https://orcid.org/0000-0003-3111-2665)
- Yinyin Yuan
- Pedro Oliveira (ORCID: https://orcid.org/0000-0001-8912-2490)
- Mohammed S. Khalil (ORCID: https://orcid.org/0000-0002-1539-5629)
- Claire Wilson (ORCID: https://orcid.org/0000-0002-6401-2014)
- Piotr Pawlik (ORCID: https://orcid.org/0009-0008-7075-615X)
- Judith Cave
- Mo Asif
- Asia Ahmed
- Jack French
- Katherine D. Brown
- Siow Ming Lee
- Anne-Marie Hacker
- Eustace Fontaine
- Kevin G. Blyth
- H. E. Stevens
- Vijay V. Joshi
- J. M. Boissiere
- Dean A. Fennell
- Robert Bentham
- Simon Jordan
- Tanya Ahmad
- Anand Devaraj
- Monica Sivakumar
- Mandeesh Sangha
- J. C. Ambrose
- Magali N. Taylor
- S. Harries
- Stephan Beck
- W. Spooner
- Kayleigh Gilbert
- Craig Dick
- Steve Bandula
- D. Perez-Gil
- Mansi Shah
- Hema Chavan
- T. Rogers
- Petra Georg
- Karl S. Peggs
- Lyn Ambrose
- Peter Russell
- Andrew Rowan
- Emilia L. Lim (ORCID: https://orcid.org/0009-0009-2954-1795)
- Keith M. Kerr
- C. E. H. Craig
- Sarah Booth
- Ellen Thomas
- Leena Dennis Joseph (ORCID: https://orcid.org/0000-0002-9395-2961)
- David Chuter
- Michalina Magala
Institutions
- Semmelweis University (HU)
- Eötvös Loránd University (HU)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- University College Hospital (GB)
- Swansea Bay University Health Board (GB)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- Garvan Institute of Medical Research (AU)
- Institute of Cancer Research (GB)
- University of Liverpool (GB)
- University of Leicester (GB)
- Queen Mary University of London (GB)
- Royal Free London NHS Foundation Trust (GB)
- University of Cologne (DE)
- University of Aberdeen (GB)
- Guy's and St Thomas' NHS Foundation Trust (GB)
- Aarhus University (DK)
- Max Delbrück Center (DE)
- NHS Greater Glasgow and Clyde (GB)
- Singleton Hospital (GB)
- Peter MacCallum Cancer Centre (AU)
- Aberdeen Royal Infirmary (GB)
- Princess Alexandra Hospital NHS Trust (GB)
- The Francis Crick Institute (GB)
- Royal London Hospital (GB)
- Cancer Research UK (GB)
- Buda Health Center (HU)
- Golden Jubilee National Hospital (GB)
- Aarhus University Hospital (DK)
- University Hospitals of Leicester NHS Trust (GB)
- Whittington Hospital (GB)
- Harefield Hospital (GB)
- University Hospital Southampton NHS Foundation Trust (GB)
- University of Surrey (GB)
- University of Manchester (GB)
- Maastricht University (NL)
- Liverpool Heart and Chest Hospital (GB)
- London Cancer (GB)
- VIB-KU Leuven Center for Cancer Biology (BE)
- Manchester University NHS Foundation Trust (GB)
- NHS Grampian (GB)
- Sheffield Teaching Hospitals NHS Foundation Trust (GB)
- VIB-KU Leuven Center for Microbiology (BE)
- Dana-Farber Cancer Institute (US)
- NIHR Southampton Biomedical Research Centre (GB)
- Cancer Research UK Manchester Institute (GB)
- The Christie NHS Foundation Trust (GB)
- National Cancer Centre Singapore (SG)
- Cancer Research UK Scotland Institute (GB)
- Genomics England (GB)
- Immune Regulation (United Kingdom) (GB)
- Royal Surrey NHS Foundation Trust (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- Danish Cancer Society (DK)
- William Harvey Research Institute (GB)
- Wythenshawe Hospital (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Genomics (United Kingdom) (GB)
- University Hospital Cologne (DE)
- Institute of Structural and Molecular Biology (GB)
- Queen Elizabeth University Hospital (GB)
- Dana-Farber Brigham Cancer Center (US)
- The Patients Association (GB)
- Toranomon Hospital (JP)
- Cancer Research UK Manchester Centre
- Berlin Institute for the Foundations of Learning and Data (DE)
- University College London (GB)
- Imperial College London (GB)
- Mass General Brigham (US)
- University of Glasgow (GB)
- University of Birmingham (GB)
- University of Sheffield (GB)
- Stanford University (US)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Genetics
- Published
- 2025-02-18
- DOI
- https://doi.org/10.1038/s41588-025-02086-5
- Citations
- 7
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 4.78
Funders
- Medical Research Council