ImmuneLENS characterizes systemic immune dysregulation in aging and cancer
Authors: Bentham Robert , Jones Thomas P. , Black James R. M. , Martinez-Ruiz Carlos , Dietzen Michelle , Litovchenko Maria , Thol Kerstin , Watkins Thomas B. K. , Bailey Chris , Pich Oriol , Zhang Zhihui , Van Loo Peter ,   TRACERx Consortium, Jamal-Hanjani Mariam , Martínez-Ruiz Carlos , Van Loo Peter , Black James R. M. , Karasaki Takahiro , Bunkum Abigail , Hessey Sonya , Liu Wing Kin , Birkbak Nicolai J. , Frankell Alexander M. , Huebner Ariana , Puttick Clare , Hiley Crispin T. , Moore David A. , Biswas Dhruva , Lim Emilia L. , Grigoriadis Kristiana , Bakir Maise Al , Lucas Olivia , Vendramin Roberto , Ward Sophia , Harries Sian , Zaccaria Simone , Zaidi Rija , Patruno Lucrezia , Karagianni Despoina , Quezada Sergio A. , Bola Supreet Kaur , Forster Martin D. , Lee Siow Ming , Richard Corentin , Naceur-Lombardelli Cristina , Gimeno-Valiente Francisco , Thakkar Krupa , Sivakumar Monica , Kanu Nnennaya , Usaite Ieva , Saghafinia Sadegh , Veeriah Selvaraju , Vanloo Sharon , Toncheva Antonia , Prymas Paulina , Mussa Bushra , Magala Michalina , Keene Elizabeth , Leung Michelle M. , Wilson Gareth A. , Rosenthal Rachel , Rowan Andrew , Lee Claudia , Colliver Emma , Enfield Katey S. S. , Angelova Mihaela , Murphy Cian , Zagorulya Maria , Marafioti Teresa , Borg Elaine , Falzon Mary , Khiroya Reena , Wong Yien Ning Sophia , Hoogenboom Emilie Martinoni , Monk Fleur , Holding James W. , Choudhary Junaid , Bhakhri Kunal , Gorman Pat , Stephens Robert C. M. , Pisciella Maria Chiara , Bandula Steve , Nicod Jerome , Dwornik Angela , Karamani Angeliki , Chain Benny , Pearce David R. , Stavrou Georgia , Mastrokalos Gerasimos-Theodoros , Lowe Helen L. , Reading James L. , Hartley John A. , Selvaraju Kayalvizhi , Ensell Leah , Shah Mansi , Pawlik Piotr , Gamble Samuel , Ung Seng Kuong Anakin , Spanswick Victoria , Wu Yin , Lester Jason F. , Dulloo Sean , Fennell Dean A. , Bajaj Amrita , Nakas Apostolos , Sodha-Ramdeen Azmina , Tufail Mohamad , Scotland Molly , Boyles Rebecca , Rathinam Sridhar , Wilson Claire , Matharu Gurdeep , Shaw Jacqui A. , Boleti Ekaterini , Cheyne Heather , Khalil Mohammed , Richardson Shirley , Cruickshank Tracey , Price Gillian , Kerr Keith M. , Benafif Sarah , Papadatos-Pastos Dionysis , Wilson James , Ahmad Tanya , French Jack , Gilbert Kayleigh , Naidu Babu , Patel Akshay J. , Middleton Gary , Osman Aya , Sangha Mandeesh , Langman Gerald , Shackleford Helen , Djearaman Madava , Leek Angela , Hodgkinson Jack Davies , Totton Nicola , Crosbie Philip , Fontaine Eustace , Granato Felice , Novasio Juliette , Rammohan Kendadai , Joseph Leena , Bishop Paul , Joshi Vijay , Waplington Sara , Atkin Adam , Brown Katherine D. , Carter Mathew , Chaturvedi Anshuman , Oliveira Pedro , Lindsay Colin R. , Blackhall Fiona H. , Summers Yvonne , Krebs Matthew G. , Paiva-Correia Antonio , Tugwood Jonathan , Dive Caroline , Aerts Hugo J. W. L. , Schwarz Roland F. , Kaufmann Tom L. , Szallasi Zoltan , Diossy Miklos , Salgado Roberto , Demeulemeester Jonas , Castignani Carla , Beck Stephan , Kassiotis George , Noorani Imran , Weeden Clare E. , Grönroos Eva , Goldman Jacki , Escudero Mickael , Hobson Philip , Boeing Stefan , Denner Tamara , Barbè Vittorio , Lu Wei-Ting , Hill William , Naito Yutaka , Sahai Erik , Ramsden Zoe , Nye Emma , Stone Richard Kevin , Rane Jayant K. , Kittel Jeanette , Haase Kerstin , Koh Kexin , Scott Rachel , Peggs Karl S. , Veiga Catarina , Royle Gary , Collins-Fekete Charles-Antoine , Fraioli Francesco , Ashford Paul , Nair Arjun , Procter Alexander James , Ahmed Asia , Taylor Magali N. , Lawrence David , Patrini Davide , Navani Neal , Thakrar Ricky M. , Janes Sam M. , Kaplar Zoltan , Hackshaw Allan , Pilotti Camilla , Leslie Rachel , Hacker Anne-Marie , Smith Sean , Walker Aoife , Grapa Anca , Zhang Hanyun , AbdulJabbar Khalid , Pan Xiaoxi , Yuan Yinyin , Chuter David , MacKenzie Mairead , Chee Serena , Georg Patricia , Alzetani Aiman , Cave Judith , Lim Eric , Nicholson Andrew G. , De Sousa Paulo , Jordan Simon , Rice Alexandra , Raubenheimer Hilgardt , Bhayani Harshil , Ambrose Lyn , Devaraj Anand , Chavan Hema , Begum Sofina , Buderi Silviu I. , Kaniu Daniel , Malima Mpho , Booth Sarah , Fernandes Nadia , Shah Pratibha , Proli Chiara , Hewish Madeleine , Danson Sarah , Shackcloth Michael J. , Robinson Lily , Russell Peter , Blyth Kevin G. , Kidd Andrew , Dick Craig , Le Quesne John , Kirk Alan , Asif Mo , Bilancia Rocco , Kostoulas Nikos , Whiteley Jennifer , Thomas Mathew ,   Genomics England Consortium, Ambrose J. C. , Arumugam P. , Baple E. L. , Bleda M. , Boardman-Pretty F. , Boissiere J. M. , Boustred C. R. , Brittain H. , Caulfield M. J. , Chan G. C. , Craig C. E. H. , Daugherty L. C. , de Burca A. , Devereau A. , Elgar G. , Foulger R. E. , Fowler T. , Furió-Tarí P. , Hackett J. M. , Halai D. , Hamblin A. , Henderson S. , Holman J. E. , Hubbard T. J. P. , Ibáñez K. , Jackson R. , Jones L. J. , Kasperaviciute D. , Kayikci M. , Lahnstein L. , Lawson L. , Leigh S. E. A. , Leong I. U. S. , Lopez F. J. , Maleady-Crowe F. , Mason J. , McDonagh E. M. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A. C. , Odhams C. A. , Patch C. , Perez-Gil D. , Polychronopoulos D. , Pullinger J. , Rahim T. , Rendon A. , Riesgo-Ferreiro P. , Rogers T. , Ryten M. , Savage K. , Sawant K. , Scott R. H. , Siddiq A. , Sieghart A. , Smedley D. , Smith K. R. , Sosinsky A. , Spooner W. , Stevens H. E. , Stuckey A. , Sultana R. , Thomas E. R. A. , Thompson S. R. , Tregidgo C. , Tucci A. , Walsh E. , Watters S. A. , Welland M. J. , Williams E. , Witkowska K. , Wood S. M. , Zarowiecki M. , Swanton Charles , McGranahan Nicholas 
Published: February 2025

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.