{Reference Type}: Journal Article
{Title}: ZNF683 marks a CD8+ T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome.
{Author}: Parry EM;Lemvigh CK;Deng S;Dangle N;Ruthen N;Knisbacher BA;Broséus J;Hergalant S;Guièze 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;
{Journal}: Cancer Cell
{Volume}: 41
{Issue}: 10
{Year}: 2023 10 9
{Factor}: 38.585
{DOI}: 10.1016/j.ccell.2023.08.013
{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.