%0 Journal Article
%T ZNF683 marks a CD8+ T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome.
%A Parry EM
%A Lemvigh CK
%A Deng S
%A Dangle N
%A Ruthen N
%A Knisbacher BA
%A Broséus J
%A Hergalant S
%A Guièze R
%A Li S
%A Zhang W
%A Johnson C
%A Long JM
%A Yin S
%A Werner L
%A Anandappa A
%A Purroy N
%A Gohil S
%A Oliveira G
%A Bachireddy P
%A Shukla SA
%A Huang T
%A Khoury JD
%A Thakral B
%A Dickinson M
%A Tam C
%A Livak KJ
%A Getz G
%A Neuberg D
%A Feugier P
%A Kharchenko P
%A Wierda W
%A Olsen LR
%A Jain N
%A Wu CJ
%J Cancer Cell
%V 41
%N 10
%D 2023 10 9
%M 37738974
%F 38.585
%R 10.1016/j.ccell.2023.08.013
%X 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.