GABA promotes resistance to immunotherapy in patients with TLS-positive tumors

Tumor-derived gamma-aminobutyric acid (GABA) drives immunotherapy resistance in TLS-positive tumors by inducing tertiary lymphoid structure dysfunction and suppressing B cell activity through GABAB receptor signaling and metabolic reprogramming. Integrated spatial and functional analyses by Hernández-Verdin et al. demonstrated that GABA disrupts the immune microenvironment within these otherwise favorable structures. Inhibition of GABA synthesis restored immune infiltration and improved therapeutic efficacy, identifying GABA as a druggable target to overcome checkpoint inhibitor resistance.