Molecular Checkpoints of Nucleic Acid Sensing in Tumor Cells: Linking Innate Immune Evasion to Precision Cancer Immunotherapy
4 affiliations
- 1Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai 200040, China
- 2Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
- 3School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
- 4Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
Abstract
Tumor cells possess nucleic-acid sensing systems that detect aberrant DNA and RNA arising from genomic and transcriptomic dysregulation. Cytosolic DNA and RNA sensors, together with endosomal nucleic acid sensors, can induce type I interferons, inflammatory chemokines, antigen presentation programs, and immune cell recruitment. Yet many tumors remain immunologically silent despite harboring potentially immunostimulatory nucleic acids, indicating that malignant cells can restrain these pathways at multiple levels. Nucleic acid clearance, selective RNA editing and remodeling, extracellular second messenger degradation, and epigenetic silencing can suppress these responses. These regulatory layers may favor immune-poor tumor states and limit responsiveness to immune checkpoint blockade. Therapeutic reactivation must be spatially and temporally controlled, because persistent signaling can undergo maladaptive rewiring. We review these molecular brakes, therapeutic strategies to restore innate sensing, and a proposed biomarker framework integrating sensor competence, suppressor activity, and functional immune output. We distinguish the effects arising within tumor cells from those mediated by sensing mechanisms in neighboring host cells and discuss cellular and spatial context, signaling dynamics, and safety. The proposed framework for matching treatments to patients remains investigational and requires prospective clinical validation.
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BibTeX
@article{wang2026molecular,
title = {{Molecular Checkpoints of Nucleic Acid Sensing in Tumor Cells: Linking Innate Immune Evasion to Precision Cancer Immunotherapy}},
author = {Yan Wang and Bowei Cao and Huili Lu and Zhicheng Wang and Yanli Qin},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219417},
url = {https://www.mdpi.com/1422-0067/27/21/9417},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular Checkpoints of Nucleic Acid Sensing in Tumor Cells: Linking Innate Immune Evasion to Precision Cancer Immunotherapy
AU - Yan Wang
AU - Bowei Cao
AU - Huili Lu
AU - Zhicheng Wang
AU - Yanli Qin
PY - 2026
DA - 2026/10/22
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219417
UR - https://www.mdpi.com/1422-0067/27/21/9417
AB - Tumor cells possess nucleic-acid sensing systems that detect aberrant DNA and RNA arising from genomic and transcriptomic dysregulation. Cytosolic DNA and RNA sensors, together with endosomal nucleic acid sensors, can induce type I interferons, inflammatory chemokines, antigen presentation programs, and immune cell recruitment. Yet many tumors remain immunologically silent despite harboring potentially immunostimulatory nucleic acids, indicating that malignant cells can restrain these pathways at multiple levels. Nucleic acid clearance, selective RNA editing and remodeling, extracellular second messenger degradation, and epigenetic silencing can suppress these responses. These regulatory layers may favor immune-poor tumor states and limit responsiveness to immune checkpoint blockade. Therapeutic reactivation must be spatially and temporally controlled, because persistent signaling can undergo maladaptive rewiring. We review these molecular brakes, therapeutic strategies to restore innate sensing, and a proposed biomarker framework integrating sensor competence, suppressor activity, and functional immune output. We distinguish the effects arising within tumor cells from those mediated by sensing mechanisms in neighboring host cells and discuss cellular and spatial context, signaling dynamics, and safety. The proposed framework for matching treatments to patients remains investigational and requires prospective clinical validation.
SN - 1422-0067
ER -