ZNF683 marks a CD8 T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome.
Fiche publication
Date publication
septembre 2023
Journal
Cancer cell
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FEUGIER Pierre
Tous les auteurs :
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 J, 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
Lien Pubmed
Résumé
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 T cells with response.
Mots clés
Hobit, PD-1, Richter transformation, ZNF683, checkpoint blockade, chronic lymphocytic leukemia, immunotherapy, single-cell RNA sequencing, t cells, tox
Référence
Cancer Cell. 2023 09 19;: