Projects per year
Abstract
Focal Adhesion Kinase (FAK) inhibitors are currently undergoing clinical testing in combination with anti-PD-1 immune checkpoint inhibitors. However, which patients are most likely to benefit from FAK inhibitors, and what the optimal FAK/immunotherapy combinations are, is currently unknown. We identify that cancer cell expression of the T-cell co-stimulatory ligand CD80 sensitizes murine tumors to a FAK inhibitor and show that CD80 is expressed by human cancer cells originating from both solid epithelial cancers and some hematological malignancies in which FAK inhibitors have not been tested clinically. In the absence of CD80, we identify that targeting alternative T-cell co-stimulatory receptors, in particular OX-40 and 4-1BB in combination with FAK, can drive enhanced anti-tumor immunity and even complete regression of murine tumors. Our findings provide rationale supporting the clinical development of FAK inhibitors in combination with patient selection based on cancer cell CD80 expression, and alternatively with therapies targeting T-cell co-stimulatory pathways.
Original language | English |
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Article number | e48092 |
Journal | eLIFE |
Volume | 9 |
Early online date | 21 Jan 2020 |
DOIs | |
Publication status | E-pub ahead of print - 21 Jan 2020 |
Keywords / Materials (for Non-textual outputs)
- FAK
- immunotherapy
- cancer
- T-cell co-stimunation
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Dive into the research topics of 'T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity'. Together they form a unique fingerprint.Projects
- 2 Finished
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Defining the mechanisms of FAK-dependent immune evasion in Pancreatic Cancer
Serrels, A. (Principal Investigator)
1/10/18 → 30/09/24
Project: Research
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Inflammatory mechanisms to suppress Treg cell function in cancer
Anderton, S. (Principal Investigator) & Serrels, A. (Co-investigator)
1/11/16 → 30/04/20
Project: Research
Equipment
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Institute for Regeneration and Repair Flow Cytometry Facility
Johnston, S. (Manager), Rossi, F. (Manager), Cryer, C. (Other) & Laird, A. (Other)
Institute of Regeneration and RepairFacility/equipment: Facility