Histone deacetylases inhibitor chidamide synergizes with humanized PD1 antibody to enhance T-cell chemokine expression and augment Ifn-γ response in NK-T cell lymphoma.

ABSTRACT:

Background

Whether immunotherapy combined with different histone deacetylases (HDAC) inhibitors in refractory or relapsed natural killer/T-cell lymphoma (NKTCL) is superior to each agent is still lacking in head-to-head clinical trials or preclinical evidence.

Methods

NKTCL cell line xenograft models (CDX) in immunocompetent, human programmed cell death protein 1 (PD1) knock-in genetically engineered mice were used to investigate the combination effects. Different types and dosages of HDAC inhibitors were investigated. We explored the underlying mechanisms by RNA-sequencing and ChIP-sequencing. Two clinical cases treated with anti-PD1/chidamide were presented.

Findings

Anti-PD1/chidamide shows significant tumour rejection in two CDX models. RNA-seq and CHIP-seq reveal

SUBMITTER: Wen T 

PROVIDER: S-EPMC9823149 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature