Student and Faculty Publications
Publication Date
10-9-2023
Journal
Cancer Cell
Abstract
Unlike many other hematologic malignancies, Richter syndrome (RS), an aggressive B cell lymphoma originating from indolent chronic lymphocytic leukemia, is responsive to PD-1 blockade. To discover the determinants of response, we analyze single-cell transcriptome data generated from 17 bone marrow samples longitudinally collected from 6 patients with RS. Response is associated with intermediate exhausted CD8 effector/effector memory T cells marked by high expression of the transcription factor ZNF683, determined to be evolving from stem-like memory cells and divergent from terminally exhausted cells. This signature overlaps with that of tumor-infiltrating populations from anti-PD-1 responsive solid tumors. ZNF683 is found to directly target key T cell genes (TCF7, LMO2, CD69) and impact pathways of T cell cytotoxicity and activation. Analysis of pre-treatment peripheral blood from 10 independent patients with RS treated with anti-PD-1, as well as patients with solid tumors treated with anti-PD-1, supports an association of ZNF683high T cells with response.
Keywords
Humans, Leukemia, Lymphocytic, Chronic, B-Cell, CD8-Positive T-Lymphocytes, Lymphoma, Large B-Cell, Diffuse, Gene Expression Regulation, Immunotherapy, Richter’s transformation, chronic lymphocytic leukemia, immunotherapy, PD-1, checkpoint blockade, T cells, ZNF683, Hobit, Tox, single-cell RNA sequencing
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
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Associated Data
PMID: 37738974