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