Dexmedetomidine induces immunogenic cancer cell death and sensitizes tumors to PD-1 blockade.

ABSTRACT:

Background

Local anesthetics promote anticancer immune responses. A machine learning-based algorithm trained with information on the biological effects and molecular descriptors of analgesics, anesthetics, hypnotics and opioids predicted antitumor effects for dexmedetomidine (DEX). DEX is a sedative acting as an alpha2-adrenoceptor (ADRA2) agonist. Based on these premises, we investigated the putative antineoplastic effects of DEX.

Results

In vitro, DEX promoted premortem stresses such as autophagy and partial endoplasmic reticulum stress with the phosphorylation of eukaryotic initiation factor 2 alpha and the inhibition of the splicing of X-box binding protein 1. DEX elicited the biomarkers of immunogenic cell death, including the release of ATP and high-mobility group box

SUBMITTER: Zhao L 

PROVIDER: S-EPMC12142037 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature