Related Experiment Video
Updated: Jan 23, 2026
Monitoring the Cancer-Immunity Cycle and Exploring Tumor Microenvironment Dynamics
Published on: June 7, 2024
ADAR and Immune Silencing in Cancer
1Discovery, InsideOutBio, 42 8th Street, Unit 3412, Charlestown, MA 02129, USA.
Abstract:
The regulation of immune responses by tumors is central to their survival. By diminishing the production of interferon (IFN) and other inflammatory mediators, tumors enhance immune evasion. Responses initiated by nucleic acid sensors and triggered by dysregulated RNA transcription and cytoplasmic DNA undergo down-modulation in tumors. A protein hub that involves the double-stranded RNA (dsRNA) editing enzyme adenosine deaminase RNA specific (ADAR), the RNase DICER1, and the dsRNA-activated kinase protein activator of PKR (PACT) mediates many of these tumor-intrinsic responses, with in vitro ADAR dependency varying by tumor type (range 11-80%). The central role played by ADAR, both as an enzyme and as a scaffold, sets it as a target for cancer immunotherapy. Therapeutic approaches focusing on the ADAR p150 isoform and its Z-DNA- and Z-RNA-specific Zα domain find support from recent mouse and human studies.
Insights
Tumors evade immune detection by suppressing inflammatory signals. A protein complex including ADAR enzyme is key, making it a potential target for novel cancer immunotherapies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumors regulate immune responses to survive, often by reducing interferon (IFN) and inflammatory mediators.
- This immune evasion involves down-modulation of nucleic acid sensor pathways triggered by RNA and DNA within tumor cells.
Purpose of the Study:
- To investigate the role of a specific protein hub in tumor-intrinsic immune regulation and its potential as a cancer immunotherapy target.
Main Methods:
- Analysis of a protein complex involving adenosine deaminase RNA specific (ADAR), DICER1, and protein activator of PKR (PACT).
- In vitro assessment of ADAR dependency across different tumor types.
Main Results:
- A protein hub comprising ADAR, DICER1, and PACT mediates tumor-intrinsic immune suppression.
- ADAR dependency varied significantly (11-80%) across tumor types, highlighting its central role.
- ADAR's dual function as an enzyme and scaffold positions it as a viable immunotherapy target.
Conclusions:
- ADAR plays a critical role in tumor immune evasion.
- Targeting ADAR, particularly the p150 isoform and its Zα domain, shows promise for developing new cancer immunotherapies.
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