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ImmuneLENS characterizes systemic immune dysregulation in aging and cancer.

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posted on 2025-03-19, 10:19 authored by Robert Bentham, Thomas P Jones, James RM Black, Carlos Martinez-Ruiz, Michelle Dietzen, Maria Litovchenko, Kerstin Thol, Thomas BK Watkins, Chris Bailey, Oriol Pich, Zhihui Zhang, Peter Van Loo, TRACERx Consortium, Genomics England Consortium, Charles Swanton, Nicholas McGranahan
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.

Funding

Crick (Grant ID: CC2041, Grant title: Swanton CC2041) Crick (Grant ID: CC1119, Grant title: STP Scientific Computing) Crick (Grant ID: CC1064, Grant title: STP Genomics) Crick (Grant ID: CC1062, Grant title: STP Flow Cytometry) Crick (Grant ID: CC1061, Grant title: STP Experimental Histopathology) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: CC2040, Grant title: Sahai CC2040) Crick (Grant ID: CC2088, Grant title: Kassiotis CC2088) Novo Nordisk UK Research Foundation (Grant ID: NNF15OC0016584, Grant title: NovoNordisk Foundation 16584) European Research Council (Grant ID: 835297 - PROTEUS, Grant title: ERC 835297 - PROTEUS)

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