ArticleCell reports. Medicine2025
Potentiating anti-tumor immunity by re-engaging immune synapse molecules.
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
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- Integrative multi-omics identifies a diagnostic T cell signature for cutaneous squamous cell carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
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- Lactate-mediated NK cell dysfunction as a prognostic marker and therapeutic target in breast cancer.Cell death discovery · 2026Article
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- Dual-module aCAR-iCAR NK cells for solid tumors: cascade resistance mechanisms, AI-driven engineering, and precision stratification.Frontiers in immunology · 2026Review
- Spontaneous Carcinoogenesis: Regulation of Adhesion Disorders and Cancer Prevention.Bulletin of experimental biology and medicine · 2025Article
- Association of Neuronal Autoantibodies with Overall Survival in Patients with Gastric Cancer.Cancer research communications · 2025Article
- MiR-518c-5p/miR-4524a-3p can mediate immune escape and chemotherapy resistance in triple-negative breast cancer and predict its outcome.Hereditas · 2025Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- UHRF1 in Immune Regulation and Diseases: Mechanisms and Therapeutic Implications.Clinical reviews in allergy & immunology · 2025Review
- Causal Inference and Shared Molecular Pathways in Crohn's Disease, Celiac Disease, and Ankylosing Spondylitis: Integrative Mendelian Randomization and Transcriptomic Analysis.International journal of molecular sciences · 2025Article
- Integrin alpha L: structure, cellular functions, and emerging role in human diseases.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The formation of immune synapses (ISs) between cytotoxic T cells and tumor cells is crucial for effective tumor elimination. However, the role of ISs in immune evasion and resistance to immune checkpoint blockades (ICBs) remains unclear. We demonstrate that ICAM-1, a key IS molecule activating LFA-1 signaling in T and natural killer (NK) cells, is often expressed at low levels in cancers. The absence of ICAM-1 leads to significant resistance to T and NK cell-mediated anti-tumor immunity. Using a CRISPR screen, we show that ICAM-1 is epigenetically regulated by the DNA methylation pathway involving UHRF1 and DNMT1. Furthermore, we engineer an antibody-based therapeutic agent, "LFA-1 engager," to enhance T cell-mediated anti-tumor immunity by reconstituting LFA-1 signaling. Treatment with LFA-1 engagers substantially enhances immune-mediated cytotoxicity, potentiates anti-tumor immunity, and synergizes with ICB in mouse models of ICAM-1-deficient tumors. Our data provide promising therapeutic strategies for re-engaging immune stimulatory signals in cancer immunotherapy.
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