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Updated: Jan 8, 2026
11:11
Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment
Published on: January 24, 2020
11.4K
A TAK1 cytokine toxicity checkpoint controls anti-cancer immunity
Tirta M Djajawi1, Anne Huber1, Sarahi Mendoza Rivera2
1Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Melbourne, VIC 3086, Australia.
Cell Reports
|December 20, 2025
Summary
Transforming growth factor beta-activated kinase 1 (TAK1) protects cancer cells from immune attack. Inhibiting TAK1 enhances cancer immunotherapy by making tumors more susceptible to T cell-mediated killing.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Cancer immunotherapies show limited efficacy in many patients.
- Tumor-intrinsic mechanisms of immune evasion require further elucidation.
Purpose of the Study:
- Identify novel tumor-intrinsic checkpoints regulating immune evasion.
- Investigate the role of MAP3K7 (TAK1) in protecting cancer cells from T cell-mediated killing.
Main Methods:
- Kinome-wide CRISPR-Cas9 screening.
- Analysis of TNF and IFNγ signaling pathways.
- Inhibition of TAK1 in cancer cell lines and mouse models.
- Adoptive T cell therapy experiments.
Main Results:
- TAK1 was identified as a critical checkpoint protecting cancer cells from CD8+ T cell killing.
- TAK1 inhibition redirects TNF/IFNγ signaling towards apoptosis and enhances IFNγ priming.
- TAK1 loss leads to cFLIP degradation and promotes apoptosis via RIPK1 and caspase-8.
- TAK1-deficient tumors showed impaired growth in immune-competent mice and were susceptible to adoptive T cell therapy.
Conclusions:
- TAK1 acts as a tumor-intrinsic immune checkpoint.
- TAK1 inhibition is a promising strategy to enhance cancer immunotherapy efficacy.
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