Melanoma Cell Intrinsic GABA_A Receptor Enhancement Potentiates Radiation and Immune Checkpoint Inhibitor Response by Promoting Direct and T Cell-Mediated Antitumor Activity.

ABSTRACT:

Purpose

Most patients with metastatic melanoma show variable responses to radiation therapy and do not benefit from immune checkpoint inhibitors. Improved strategies for combination therapy that leverage potential benefits from radiation therapy and immune checkpoint inhibitors are critical.

Methods and materials

We analyzed metastatic melanoma tumors in the TCGA cohort for expression of genes coding for subunits of type A γ-aminobutyric acid (GABA) receptor (GABA_AR), a chloride ion channel and major inhibitory neurotransmitter receptor. Electrophysiology was used to determine whether melanoma cells possess intrinsic GABA_AR activity. Melanoma cell viability studies were conducted to test whether enhancing GABA_AR mediated chloride transport us

SUBMITTER: Pomeranz Krummel DA 

PROVIDER: S-EPMC8329598 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature