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

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 pa

SUBMITTER: Parry EM 

PROVIDER: S-EPMC10618915 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature