Chronic lymphocytic leukemia presence impairs antigen-specific CD8⁺ T-cell responses through epigenetic reprogramming towards short-lived effectors.

ABSTRACT: T-cell dysregulation in chronic lymphocytic leukemia (CLL) associates with low response rates to autologous T cell-based therapies. How CLL affects antigen-specific T-cell responses remains largely unknown. We investigated (epi)genetic and functional consequences of antigen-specific T-cell responses in presence of CLL in vitro and in an adoptive-transfer murine model. Already at steady-state, antigen-experienced patient-derived T cells were skewed towards short-lived effector cells (SLEC) at the expense of memory-precursor effector cells (MPEC). Stimulation of these T cells in vitro showed rapid induction of effector genes and suppression of key memory transcription factors only in presence of CLL cells, indicating epigenetic regulation. This was investigated in vivo by following antigen-s

SUBMITTER: Martens AWJ 

PROVIDER: S-EPMC9851097 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature