ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
LIGHT/TNFSF14 promotes CAR-T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironment.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 57 citations in OpenAlex.
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- Progress in cell-based immunotherapies for solid tumors.Discover oncology · 2026Review
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- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- HVEM costimulatory domain boosts CAR T cell efficacy against solid tumors via enhanced TRAF-mediated TNF signaling.Cell communication and signaling : CCS · 2026Article
- C/EBPβ-induced alternative splicing of RCAN1 generates a potent TCR-T target in mesenchymal glioblastoma.Cellular & molecular immunology · 2026Article
- From TLS architecture to functional immune niches: division of labor among CAFs, HEVs, and antigen-presenting cells in cancer immunotherapy.Frontiers in immunology · 2026Review
- Pleiotropic and multicellular roles of lymphotoxin beta receptor in solid tumor immunity and therapeutic targeting.Frontiers in immunology · 2026Review
- Advancing CAR-T therapy in prostate cancer: overcoming the tumor microenvironment and enhancing efficacy.Frontiers in oncology · 2026Review
- Constructing a PANoptosis-based prognostic signature to evaluate the immune landscape and therapeutic response in clear cell renal cell carcinoma.Journal of Zhejiang University. Science. B · 2025Article
- Photocontrolled trimethoprim PROTACs targeting the eDHFR protein tag.Nature communications · 2025Article
- The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.Journal for immunotherapy of cancer · 2025Review
- CXCR3 enhanced murine chimeric antigen receptor T cells in the treatment of solid tumors.Translational cancer research · 2025Article
- CAR-T Cell Therapy for Prostate Cancer: Current Advances and Future Perspectives.Biomedicines · 2025Review
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Tertiary Lymphoid Structures Across Organs: Context, Composition, and Clinical Levers.Immunological reviews · 2025Review
- Role of tertiary lymphoid structures in the tumour microenvironment and immunotherapy response of renal cell carcinoma.Clinical and translational medicine · 2025Review
- Immunotherapy in the Treatment of Undifferentiated Pleomorphic Sarcoma and Myxofibrosarcoma.Current treatment options in oncology · 2025Review
- Dynamic remodeling of tertiary lymphoid structures in response to cancer therapy: a recent review.Cancer immunology, immunotherapy : CII · 2025Review
- Nattokinase-driven remodeling of tumor microenvironment enhances the efficacy of MSLN-targeted CAR-T cell therapy in solid tumors.Cancer immunology, immunotherapy : CII · 2025Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tertiary lymphoid structures (TLSs) in tumor tissues facilitate immune cell trafficking and cytotoxicity, which benefits survival and favorable responses in immune therapy. Here, we observed a high correlation of tumor necrosis factor superfamily member 14 (LIGHT) expression with TLS signature genes, which are all markers for immune cell accumulation and better prognosis, through retrieving RNA sequencing (RNA-seq) data from patients with cancer, suggesting the potential of LIGHT in reconstituting a high immune-infiltrated tumor microenvironment. Accordingly, LIGHT co-expressed chimeric antigen receptor T (LIGHT CAR-T) cells not only showed enhanced cytotoxicity and cytokine production but also improved CCL19 and CCL21 expression by surrounding cells. And the supernatant of LIGHT CAR-T cells promoted T cell migration in a paracrine manner. Furthermore, LIGHT CAR-T cells showed superior anti-tumor efficacy and improved infiltration in comparison with conventional CAR-T cells in immunodeficient NSG mice. Accordingly, murine LIGHT-OT-1 T cells normalized tumor blood vessels and enforced intratumoral lymphoid structures in C57BL/6 syngeneic tumor mouse models, implying the potential of LIGHT CAR-T in clinical application. Taken together, our data revealed a straightforward strategy to optimize trafficking and cytotoxicity of CAR-T cells by redirecting TLSs through LIGHT expression, which has great potential to expand and optimize the application of CAR-T therapy in solid tumors.
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