ZNF683 marks a CD8+ T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome

Parry, EM; Lemvigh, CK; Deng, S; Dangle, N; Ruthen, N; Knisbacher, BA; Broseus, J; Hergalant, S; Guieze, R; Li, S; Zhang, W; Johnson, C; Long, JM; Yin, S; Werner, L; Anandappa, A; Purroy, N; Gohil, S; Oliveira, G; Bachireddy, P; Shukla, SA; Huang, T; Khoury, JD; Thakral, B; Dickinson, M; Tam, C; Livak, KJ; Getz, G; Neuberg, D; Feugier, P; Kharchenko, P; Wierda, W; Olsen, LR; Jain, N; Wu, CJ

Author(s): Parry, EM; Lemvigh, CK; Deng, S; Dangle, N; Ruthen, N; Knisbacher, BA; Broseus, J; Hergalant, S; Guieze, R; Li, S; Zhang, W; Johnson, C; Long, JM; Yin, S; Werner, L; Anandappa, A; Purroy, N; Gohil, S; Oliveira, G; Bachireddy, P; Shukla, SA; Huang, T; Khoury, JD; Thakral, B; Dickinson, M; Tam, C; Livak, KJ; Getz, G; Neuberg, D; Feugier, P; Kharchenko, P; Wierda, W; Olsen, LR; Jain, N; Wu, CJ;
Details: Publication Year 2023-10-09,Volume 41,Issue #10,Page 1803-1816.e8
Journal Title: Cancer Cell
Publication Type: Research article
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 ZNF683(high) T cells with response.
Publisher: Cell Press
Keywords: Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/pathology; CD8-Positive T-Lymphocytes; *Lymphoma, Large B-Cell, Diffuse/drug therapy/genetics/pathology; Gene Expression Regulation; Immunotherapy; Hobit; Pd-1; Richter transformation; Znf683; checkpoint blockade; chronic lymphocytic leukemia; single-cell RNA sequencing; t cells; tox
Department(s): Clinical Haematology
PubMed ID: 37738974
Publisher's Version: https://doi.org/10.1016/j.ccell.2023.08.013
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-12-05 12:35:39

Last Modified: 2024-07-16 04:14:59