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

GABA signaling is linked to resistance to immune checkpoint inhibitors in TLS-positive tumors, with non-responders showing increased GABA-related activity.

• Why it matters: Understanding why some TLS-positive tumors resist immunotherapy is crucial, as TLS presence usually predicts better outcomes. Identifying factors like GABA that impair immune responses can improve treatment strategies.
• What they did: The study used multi-omic profiling of ccRCC and STS tumors, revealing elevated GABA signatures in non-responders, and conducted in vitro and in vivo experiments to examine GABA’s immunosuppressive effects and potential for therapeutic targeting.
• The result: Blocking GABA synthesis enhanced immunotherapy efficacy and immune cell infiltration in mouse models, suggesting that targeting GABA could overcome resistance and improve patient responses to ICIs.