Multiomic analysis identifies epigenome alterations and effector-memory CD8+ T cell clonotypes associated with ALL disease progression 4323

Abstract Description Blood serves as a valuable biospecimen due to its ability to provide clinical insights. Peripheral blood mononuclear cells (PBMCs) can be readily isolated and are frequently used to monitor clinical progression and explore mechanisms of disease. Multiomic analyses provide powerful insights by linking open chromatin regions accessible to regulatory elements with gene expression. Here, PBMCs were profiled from a healthy and a diseased Acute Lymphoblastic Leukemia (ALL) donor at two timepoints six months apart. Analysis used 10x Genomics’ Single Cell Multiome ATAC + Gene Expression platform, enabling single cell RNA (scRNA-seq) and single cell ATAC sequencing (scATAC-seq) to profile transcriptomic and epigenomic landscapes simultaneously. Full-length T-cell receptor (TCR) sequences linked to clinical progression were also characterized using 10x Genomics’ GEM-X Immune Profiling technology. Over six months, profiling over 15,000 PBMCs, we identified an increase in naive B cells and a reduction in CD8+ effector-memory T cells, with a notable decline in the two most prominent TCR clonotypes, highlighting an altered adaptive immune response during disease progression. Parallel multiomic profiling uncovered distinct regulatory networks in advanced disease involving exhaustion markers TIGIT and LAG3 within T and NK cell populations. This study, enabled by the integration of multiple single cell technologies, provides critical insights into immune mechanisms driving cancer. Topic Categories Technological Innovations in Immunology (TECH)