ArticleProceedings of the National Academy of Sciences of the United States of America2022
Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- Genotype-driven variations in lncRNA expression underlie predisposition to high-grade serous ovarian cancer.Journal of advanced research · 2026Article
- Natural killer cells in ovarian cancer therapy: mechanisms, evasion, and therapeutic innovations.Inflammopharmacology · 2026Review
- Tumor FAK supports fibrillar collagen expression in ovarian cancer ascites.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Metabolic licensing of quiescent glioblastoma activation and immune evasion via astrocyte-mitochondria shuttle.Nature communications · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Piperlongumine inhibits the proliferation and migration of non-small cell lung cancer cells through the EGFR/FAK/STAT3 pathway.Molecular biology reports · 2026Article
- Disarming cancer resistance: FAK as a therapeutic target.Trends in cancer · 2026Review
- FAK inhibition in ovarian cancer releases omega-3 fatty acids to program CXCL13-producing anti-tumor resident peritoneal macrophages.Cell reports · 2026Article
- Activation of SV2B Inhibits Matrix-Stiffness-Induced Tumorigenesis and EMT in Glioma via FAK/PI3K/AKT Signaling Pathway.Oncology and therapy · 2026Article
- Melatonin inhibits FAK signaling to suppress PD-L1 expression and enhance chemosensitivity in triple-negative breast cancer.International journal of medical sciences · 2026Article
- Natural Killer Cell Therapy in Ovarian Cancer: From Preclinical Potentials to Clinical Applications and Combination Strategies.International journal of biological sciences · 2026Review
- From TLS architecture to functional immune niches: division of labor among CAFs, HEVs, and antigen-presenting cells in cancer immunotherapy.Frontiers in immunology · 2026Review
- The PVR-TIGIT/CD96/CD226 axis: a novel immune checkpoint target in ovarian cancer.Frontiers in immunology · 2026Review
- Unraveling tissue-specific molecular targets of dihydroartemisinin in non-small cell lung cancer: an integrative machine learning and network pharmacology approach.Medical oncology (Northwood, London, England) · 2025Article
- HSP47 inhibition-induced CD155 expression through TRAF2 deubiquitination promotes tumor immune evasion.Journal for immunotherapy of cancer · 2025Article
- Ovarian Tumor FAK Inhibition Releases Omega-3 Fatty Acids Stimulating GATA6 Peritoneal Macrophage CXCL13 Production Enhancing Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Article
- Inducible FAK loss but not FAK inhibition in endothelial cells of PYK2-null mice activates p53 tumor suppressor to prevent tumor growth.Molecular biology of the cell · 2025Article
- Bispecific antibody targeting CD155 mediates T-cell immunotherapy against human gynecological malignancies.Investigational new drugs · 2025Article
- Focal adhesion kinase-mediated interaction between tumor and immune cells in the tumor microenvironment: implications for cancer-associated therapies and tumor progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by an immunosuppressive tumor microenvironment containing few tumor infiltrating lymphocytes (TILs) and an insensitivity to checkpoint inhibitor immunotherapies. Gains in the PTK2 gene encoding focal adhesion kinase (FAK) at Chr8 q24.3 occur in ∼70% of HGSOC tumors, and elevated FAK messenger RNA (mRNA) levels are associated with poor patient survival. Herein, we show that active FAK, phosphorylated at tyrosine-576 within catalytic domain, is significantly increased in late-stage HGSOC tumors. Active FAK costained with CD155, a checkpoint receptor ligand for TIGIT (T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains), in HGSOC tumors and a selective association between FAK and TIGIT checkpoint ligands were supported by patient transcriptomic database analysis. HGSOC tumors with high FAK expression were associated with low CD3 mRNA levels. Accordingly, late-stage tumors showed elevated active FAK staining and significantly lower levels of CD3+ TILs. Using the KMF (Kras, Myc, FAK) syngeneic ovarian tumor model containing spontaneous PTK2 (FAK) gene gains, the effects of tumor intrinsic genetic or oral small molecule FAK inhibitior (FAKi; VS-4718) were evaluated in vivo. Blocking FAK activity decreased tumor burden, suppressed ascites KMF-associated CD155 levels, and increased peritoneal TILs. The combination of FAKi with blocking TIGIT antibody (1B4) maintained elevated TIL levels and reduced TIGIT+ T regulatory cell levels, prolonged host survival, increased CXCL13 levels, and led to the formation of omental tertiary lymphoid structures. Collectively, our studies support FAK and TIGIT targeting as a rationale immunotherapy combination for HGSOC.
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Registered trials
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.