Your neighbors matter: Adjacent cancer cells dampen TLS function

Cancer-derived gamma-aminobutyric acid (GABA) has been identified as an immunosuppressive factor that renders tertiary lymphoid structures (TLSs) dysfunctional, explaining why some TLS-positive tumors remain resistant to immunotherapy. Hernández-Verdin et al. demonstrated that targeting GABA signaling in combination with immunotherapy reshapes both the tumor and TLS microenvironment, ultimately improving therapeutic efficacy. The findings suggest a new combinatorial strategy to overcome immunotherapy resistance in tumors that harbor TLSs but fail to respond to checkpoint blockade.