Fes-deficient macrophages enhance CD8+ T cell priming and tumour control through increased proinflammatory cytokine production and presentation
Laight, B. J.; Dmytryk, N.; Harper, D.; Zhang, C. S.; Garven, A.; Simpson, A. L.; Berman, D. M.; Kment, J.; Alotaibi, F.; Shi, C.; Gao, Y.; Vlasschaert, C.; LeBrun, D.; Tyryshkin, K.; Craig, A.; Basta, S.; Koti, M.; Greer, P. A.
Show abstract
Homeostatic immunoregulatory mechanisms that prevent adverse effects of immune overaction can serve as barriers to successful anti-cancer immunity, representing attractive targets to improve cancer immunotherapy. Here, we demonstrate a novel role of the Fes tyrosine kinase, abundantly expressed in immune cells, as an innate intracellular immune checkpoint. Host Fes-deficiency delays tumour onset in a gene dose-dependent manner and improves murine triple negative breast cancer and melanoma tumour control, survival, doxorubicin efficacy, and anti-PD-1 therapy sensitization. These effects were associated with a shift to an anti-tumourigenic tumour immune microenvironment. In vitro, we observed increased Toll-like receptor signaling, and proinflammatory cytokine production and presentation from antigen presenting cells, leading to increased T cell activation, cancer cell killing and tumour control. This study highlights Fes as a novel innate immune checkpoint with potential as a predictive biomarker for effective immune checkpoint blockade treatment, and a potential therapeutic target to improve anti-cancer immunotherapy.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- The CCL17-CCR4 axis is critical for mutant STAT6-mediated microenvironmental remodelling and therapeutic resistance in Relapsed/Refractory Diffuse Large B Cell Lymphoma 95%
- Immune modulation of innate and adaptive responses restores immune surveillance and establishes anti-tumor immunological memory 95%
- Targeting macrophages with CAR-T cells delays solid tumor progression and enhances anti-tumor immunity 94%
Similar papers in this journal
- A transgenic line that reports CSF1R protein expression provides a definitive marker for the mouse mononuclear phagocyte system 95%
- NF-κB-Inducing Kinase (NIK) Governs the Mitochondrial Respiratory Capacity, Differentiation, and Inflammatory Status of Innate Immune Cells 95%
- Interruption of thymic activity in adults improves responses to tumor immunotherapy 94%
Similar papers in this journal
- The spontaneous neoantigen-specific CD4+ T cell response to a growing tumor is functionally and phenotypically diverse. 95%
- CXCR6 by increasing retention of memory CD8 T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer 94%
- Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.