| 000 | 02925cam a2200265 4500500 | ||
|---|---|---|---|
| 005 | 20260222002600.0 | ||
| 041 | _afre | ||
| 042 | _adc | ||
| 100 | 1 | 0 |
_aLin, Hung-Yu _eauthor |
| 700 | 1 | 0 |
_aWu, Hsing-Ju _eauthor |
| 700 | 1 | 0 |
_aChu, Pei-Yi _eauthor |
| 245 | 0 | 0 | _aIgniting the Tumor: Targeting Mitochondrial Stress to Prime Breast Cancer for Immunotherapy |
| 260 | _c2025. | ||
| 500 | _a71 | ||
| 520 | _aImmunotherapy has demonstrated limited efficacy in immunologically “cold” breast cancers characterized by absent T-cell infiltration and inadequate interferon signaling. The purpose of this work is to propose and articulate a mechanistic and therapeutic framework in which mitochondrial stress is deliberately harnessed to convert immunologically “cold” breast tumors into “hot,” T cell–inflamed, immunotherapy-responsive lesions. This review synthesizes emerging evidence positioning mitochondrial stress as a strategic lever to transform these immune-excluded tumors into inflamed, therapy-responsive lesions. We examine how mitochondrial dysfunction triggers cytosolic release of mitochondrial DNA (mtDNA), a potent damage-associated molecular pattern that activates the cGAS-STING pathway, initiating type I interferon responses and secretion of T-cell-recruiting chemokines such as CCL5 and CXCL10. This axis functions as a “double-edged sword”—while acute activation converts “cold” tumors into “hot” immune-responsive states, chronic engagement drives immunosuppressive cytokine networks and therapeutic resistance, with outcomes varying across breast cancer subtypes. We explore six combination therapeutic strategies: mitochondrial poisons, radiotherapy/chemotherapy, PARP/ATR inhibitors, metabolic reprogramming agents, mitochondrial quality control modulators, and localized mitochondrial stress induction, each paired with immune checkpoint blockade. The review emphasizes “controlled ignition” as a paradigm whereby precisely dosed mitochondrial stress amplifies tumor antigenicity and favorable cytokine landscapes while avoiding chronic immunosuppression. Cytokine networks emerge as both integrators and therapeutic targets of mitochondrial-immune crosstalk. Future advances require mapping subtype-specific thresholds, developing tumor-restricted delivery systems, and implementing biomarker-guided trials to safely harness mitochondrial stress, potentially redefining these organelles as programmable immunological adjuvants in breast cancer therapy. | ||
| 690 | _abreast cancer | ||
| 690 | _acgas | ||
| 690 | _acytokines | ||
| 690 | _aimmunotherapy | ||
| 690 | _amitochondrial stress | ||
| 690 | _asting | ||
| 690 | _atumor microenvironment | ||
| 786 | 0 | _nEuropean Cytokine Network | Volume 36 | 3 | 2025-09-01 | p. 24-37 | 1148-5493 | |
| 856 | 4 | 1 | _uhttps://stm.cairn.info/revue-european-cytokine-network-2025-3-page-24?lang=en&redirect-ssocas=7080 |
| 999 |
_c1665217 _d1665217 |
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