ArticleEMBO molecular medicine2015
ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Inhibition of SPI1 by ADAP Regulates S100A8/A9 Signaling in Macrophages to Control the Development of Colitis.Inflammation · 2026Article
- Single-Cell Transcriptomics Reveals the Potential Role of GZMK+ CD8+ T Cells in Cell Senescence of Triple-Negative Breast Cancer.International journal of genomics · 2026Article
- A Trojan horse nanoplatform overcoming delivery barriers for targeted gene immunotherapy of colorectal cancer.Frontiers in bioengineering and biotechnology · 2026Article
- Epigenome-Wide Search for Distinctive Methylation Biomarkers of Endothelial and Leukocyte DNA.Epigenomes · 2025Article
- Alternative splicing immune signature for detecting HBV-related hepatocellular carcinoma in peripheral blood mononuclear cells.Biochemistry and biophysics reports · 2025Article
- Integrated bioinformatics analysis identifies cuproptosis and ferroptosis gene signatures via subgroup clustering: Prognostic and therapeutic implications in breast cancer.Biochemistry and biophysics reports · 2025Article
- Molecular control of PDPNhi macrophage subset induction by ADAP as a host defense in sepsis.JCI insight · 2025Article
- FYB1-targeted modulation of CAPG promotes AML progression.Molecular and cellular biochemistry · 2025Article
- SKAP1 Expression in Cancer Cells Enhances Colon Tumor Growth and Impairs Cytotoxic Immunity by Promoting Neutrophil Extracellular Trap Formation via the NFATc1/CXCL8 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8Cell reports. Medicine · 2024Article
- Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy.Cancers · 2024Review
- Urolithin A Hijacks ERK1/2-ULK1 Cascade to Improve CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cell softness renders cytotoxic T lymphocytes and T leukemic cells resistant to perforin-mediated killing.Nature communications · 2024Article
- Fyn, an important molecule in the brain, is a potential therapeutic target for brain tumours.Frontiers in pharmacology · 2024Review
- Expression of PD-1 and PD-L1 in Endometrial Cancer: Molecular and Clinical Significance.International journal of molecular sciences · 2023Review
- Article
- Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment.Molecular cancer · 2023Review
- FYN: emerging biological roles and potential therapeutic targets in cancer.Journal of translational medicine · 2023Review
- Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1.Journal of immunology research · 2023Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PD-1 negatively regulates CD8(+) cytotoxic T lymphocytes (CTL) cytotoxicity and anti-tumor immunity. However, it is not fully understood how PD-1 expression on CD8(+) CTL is regulated during anti-tumor immunotherapy. In this study, we have identified that the ADAP-SKAP55 signaling module reduced CD8(+) CTL cytotoxicity and enhanced PD-1 expression in a Fyn-, Ca(2+)-, and NFATc1-dependent manner. In DC vaccine-based tumor prevention and therapeutic models, knockout of SKAP55 or ADAP showed a heightened protection from tumor formation or metastases in mice and reduced PD-1 expression in CD8(+) effector cells. Interestingly, CTLA-4 levels and the percentages of tumor infiltrating CD4(+)Foxp3(+) Tregs remained unchanged. Furthermore, adoptive transfer of SKAP55-deficient or ADAP-deficient CD8(+) CTLs significantly blocked tumor growth and increased anti-tumor immunity. Pretreatment of wild-type CD8(+) CTLs with the NFATc1 inhibitor CsA could also downregulate PD-1 expression and enhance anti-tumor therapeutic efficacy. Together, we propose that targeting the unrecognized ADAP-SKAP55-NFATc1-PD-1 pathway might increase efficacy of anti-tumor immunotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.