Domatinostat favors the immunotherapy response by modulating the tumor immune microenvironment (TIME).

ABSTRACT:

Background

The efficacy of PD-(L)1 blockade depends on the composition of the tumor immune microenvironment (TIME) and is generally higher in tumors with pre-existing cytotoxic T cells (CTL) than in those with low CTL numbers. Nonetheless, a significant proportion of patients with pre-existing immunity fail to respond, indicating a therapeutic potential for combining PD-(L)1 blockade with additional immunomodulatory agents in both CTL-high and -low immune phenotypes. Here, we evaluated domatinostat (4SC-202), a class I-selective histone deacetylase (HDAC) inhibitor, for its effect on the TIME and its antitumoral efficacy using syngeneic mouse models with CTL-high or CTL-low tumors.

Methods

Domatinostat was evaluated in PD-1 blockade-insensitive CTL-low (CT26) and CTL-high (C

SUBMITTER: Bretz AC 

PROVIDER: S-EPMC6839078 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature