Xiao Lei Chen

Tumor FAK supports fibrillar collagen expression in ovarian cancer ascites

Marjaana Ojalill, Terrance J. Haanen, Safir Ullah Khan, Yichi Zhang et autres

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Abstract 7951: Ovarian tumor FAK inhibition releases omega-3 fatty acids stimulating GATA6 peritoneal macrophage CXCL13 production augmenting TIGIT immunotherapy

Xiao Lei Chen, Kevin M. Tharp, Marjaana Ojalill, Duygu Ozmadenci et autres

Abstract High grade serous ovarian cancer (HGSOC) is a lethal gynecologic malignancy due to accumulated therapy resistance. Focal adhesion kinase (FAK) expression is elevated in HGSOC, and inhibition of FAK activity (FAKi) in syngeneic ovarian tumors reduced tumor burden with elevated CXCL13 …

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Abstract 1603: Opposing control of MHC-II antigen presentation by FAK and PYK2: Implications for therapeutic intervention

Terrance J. Haanen, Xiao Lei Chen, David D. Schlaepfer

Abstract High-grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy in the U.S. and is marked by resistance to chemo- and immunotherapy. Although focal adhesion kinases (FAK and PYK2) are known to induce tumor microenvironment immunosuppression, their role in altering …

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Abstract 6491: Co-treatment with FAK and PARP inhibitors for the treatment of homologous recombination-proficient high grade serious ovarian cancer

Caree R. Carson, Breana Hill, Aarya Ghosalkar, Marjaana Ojalill et autres

Abstract High grade serous ovarian cancer (HGSOC) - the most common subtype - accounts for the greatest number of patient deaths due to late detection and frequent recurrence. Treatment for HGSOC patients begins with cytoreductive surgery followed by platinum/taxane chemotherapy and adjuvant/maintenance …

FAK inhibition in ovarian cancer releases omega-3 fatty acids to program CXCL13-producing anti-tumor resident peritoneal macrophages

Xiao Lei Chen, Kevin M. Tharp, Marjaana Ojalill, Duygu Ozmadenci et autres

High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by therapy resistance. Focal adhesion kinase (FAK) is highly expressed in HGSOC, yet its impact on tumor-immune communication remains incompletely defined. Using three syngeneic ovarian cancer models, we show that FAK inhibition …

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Ovarian Tumor FAK Inhibition Releases Omega-3 Fatty Acids Stimulating GATA6 Peritoneal Macrophage CXCL13 Production Enhancing Immunotherapy

Xiao Lei Chen, Kevin M. Tharp, Marjaana Ojalill, Duygu Ozmadenci et autres

SUMMARY High grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy in the USA due to chemo- and immuno-therapy resistance. We show that focal adhesion kinase (FAK) inhibition with ifebemtinib or tumor genetic FAK knockout (KO) in syngeneic ovarian tumor …

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Liposomal Doxorubicin, but Not Platinum-Taxane, Supports MHC-II Expression and Immune Maturation in the Ovarian Tumor Microenvironment

James Lee, Xiao Lei Chen, Duygu Ozmadenci, Elise Tahon et autres

BACKGROUND: Ovarian cancer is an immunologically cold tumor that is treated with surgery and a chemotherapy regimen of platinum agents with taxanes. Paradoxically, elevated levels of several immune markers are effective at predicting prognosis for patients with ovarian cancer, though it is …

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Inducible FAK loss but not FAK inhibition in endothelial cells of PYK2-null mice activates p53 tumor suppressor to prevent tumor growth

Xiao Lei Chen, Marjaana Ojalill, Christine Jean, Isabelle Tancioni et autres

Focal adhesion kinase (FAK) and the related tyrosine kinase PYK2 are signaling and scaffolding proteins co-expressed in endothelial cells (ECs) that regulate blood vessel function and tumor growth. As FAK-PYK2 share overlapping cellular roles, we generated PYK2−/− FAKfl/fl mice with tamoxifen-inducible EC-specific …

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Themis dominates T cell exhaustion by regulation of TCR and PD-1 signaling

Jian Tang, Xian Jia, Taoling Zeng, Yuzhou Bao et autres

Abstract T cell exhaustion is important to protect the host from immunopathology during chronic viral infection, but it also impairs T cell anti-tumor immunity 1–5 . A fundamental unresolved question is whether and how T cell exhaustion is determined at the onset …

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Figure 3 from Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma

Yichi Zhang, Marjaana Ojalill, Antonia Boyer, Xiao Lei Chen et autres

FAK nuclear localization enhances murine ovarian tumor cell survival to cisplatin. A, FAK-KO, FAK-WT, and FAK-NLS− KMF cells were evaluated for cisplatin cytotoxicity after 48 hours in culture. Shown is percent cell viability vs. cisplatin concentration (μmol/L, log10), and points are means …

Figure 7 from Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma

Yichi Zhang, Marjaana Ojalill, Antonia Boyer, Xiao Lei Chen et autres

Nuclear FAK regulation of MKP1 expression is associated with cisplatin resistance. A, KMF FAK-WT and FAK-NLS− cells were treated with increased concentrations of cisplatin (0, 10, or 20 μmol/L) for 12 hours and protein lysates were immunoblotted for GFP-FAK, MKP1, pERK, and …

Data from Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma

Yichi Zhang, Marjaana Ojalill, Antonia Boyer, Xiao Lei Chen et autres

Abstract Tumor chemotherapy resistance arises frequently and limits high-grade serous ovarian cancer (HGSOC) patient survival. Focal adhesion kinase (FAK) is an intracellular protein–tyrosine kinase encoded by PTK2, a gene that is often gained in HGSOC. Canonically, FAK functions at the cell periphery. …