HDACi combination therapy with IDO1i remodels the tumor microenvironment and boosts antitumor efficacy in colorectal cancer with microsatellite stability.

ABSTRACT:

Background

Immunotherapy for colorectal cancer (CRC) with microsatellite stability (MSS) and mismatch repair proficiency (pMMR) has shown limited success in clinical trials. The combination of immunomodulators and immune checkpoint inhibitors (ICIs) is a potential strategy for treating CRC.

Methods

Histone deacetylase (HDAC) and indoleamine 2,3-dioxygenase 1 (IDO1) expression in CRC tissues and adjacent normal tissues was analyzed via database analysis, immunohistochemistry, and western blotting. A nanodrug designated as NP-I/P was subsequently formulated, encapsulating an IDO1 inhibitor (IDO1i; namely, epacadostat) and an immunomodulatory HDAC inhibitor (HDACi; namely, panobinostat). The antitumor efficacy of the nanoparticles and their effects on tumor microenvironment fea

SUBMITTER: Liang R 

PROVIDER: S-EPMC11648303 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature