Related Experiment Video
Updated: Jul 12, 2026
07:45
Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis
Published on: January 26, 2024
Your neighbors matter: Adjacent cancer cells dampen TLS function
Nicholas J Salgia1, Jason B Muhitch2
1Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; MD-PhD Program, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, USA.
Cancer Cell
|July 9, 2026
Summary
Cancer-derived gamma-aminobutyric acid (GABA) can make tumors resistant to immunotherapy by disrupting tertiary lymphoid structures (TLSs). Targeting GABA reshapes the tumor microenvironment, improving immunotherapy effectiveness.
Area of Science:
- Immunology
- Cancer Biology
- Neuroscience
Background:
- Tertiary lymphoid structures (TLSs) are associated with immunotherapy response in some cancers.
- The mechanisms underlying immunotherapy resistance in tumors with TLSs remain incompletely understood.
Purpose of the Study:
- To investigate the role of cancer-derived factors in mediating immunotherapy resistance in tumors with TLSs.
- To identify novel targets for overcoming immunotherapy resistance.
Main Methods:
- Analysis of tumor microenvironments in preclinical cancer models.
- Assessment of gamma-aminobutyric acid (GABA) levels and function.
- Evaluation of therapeutic efficacy after targeting GABA in combination with immunotherapy.
Main Results:
- Tumors with TLSs that resist immunotherapy produce cancer-derived gamma-aminobutyric acid (GABA).
- GABA acts as an immunosuppressant, leading to dysfunctional TLS and reduced immunotherapy efficacy.
- Targeting GABA reshaped the tumor and TLS microenvironment, enhancing anti-tumor immunity.
Conclusions:
- Cancer-derived GABA is a key factor contributing to immunotherapy resistance.
- Targeting GABA presents a promising strategy to improve immunotherapy outcomes in specific cancer types.
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