Early Immune Dysfunction in CLL Reversible with Ibrutinib: A Single-Cell Study
Summary
The focus of this discourse is on an examination that implemented single-cell analysis to scrutinize the interactions between immune cells and leukemia cells in chronic lymphocytic leukemia (CLL), which is categorized as a cancer that affects lymphocytes or white blood cells. This article strives to fathom how CLL evolves from its precursor stage, which is dubbed as monoclonal B-cell lymphocytosis (MBL), and how a medication known as ibrutinib can counteract some of the immune dysfunction that is instigated by CLL. The article posits that CLL cells coexist with sundry immune cell types in the bloodstream, and these immune cells showcase manifestations of exhaustion and debilitation. Furthermore, it is asserted that ibrutinib can restore certain immune cell functions and assuage inflammation.
Research Criteria
The research idea of this article is to use single cell transcriptome sequencing to characterize the circulating immune cells co-existing with leukemic cells during natural progression of chronic lymphocytic leukemia (CLL), and to investigate how ibrutinib, a drug that inhibits a key signaling pathway in CLL cells, affects the immune dysfunction caused by CLL. The article aims to provide new insights into the co-evolution of leukemia and immune cells and the potential therapeutic benefits of ibrutinib.
Sample Type
Human PBMCs.
Result—scRNA-seq Analysis of Immune Cells from Non-Progressive MBL Patients and CLL Patients
After a median follow-up of 7.0 years, they collected serial peripheral blood mononuclear cell (PBMC) samples from three individuals with high count MBL who did not progress to CLL and seven patients with CLL. They collected paired samples from all patients: the first time point (T1) was collected at a median of 4.96 years after MBL diagnosis or 2.54 years after CLL diagnosis, and the second time point (T2) was collected at a median of 2.97 years after T1 for MBL patients and 4.75 years for CLL patients. T2 samples were collected from CLL patients a median of 0.2 years before their first treatment.
They discovered 16 clusters across three distinct lineages: T cells, NK cells, and myeloid cells. Immune cell type distribution in MBL and CLL samples and across patients appeared to be balanced across cell clusters. There were no differences in the proportions of immune cell types, including various T cell subsets, between MBL and CLL samples.
Fig.1 scRNA-seq analysis of immune cells from non-progressive MBL patients and CLL patients. (Purroy, 2022)
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Reference
- Purroy, N.; et al. Single-cell analysis reveals immune dysfunction from the earliest stages of CLL that can be reversed by ibrutinib. Blood. 2022, 139(14): 2252-2256.
