Mitochondrial metabolic reprogramming at the interface of chemoresistance and immune-cold tumor states.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic concepts without primary human data or systematic review methodology.
PubMed 42577501 · doi:10.3389/fimmu.2026.1872804
What was done
This narrative review synthesized literature examining the intersection between mitochondrial metabolic adaptations, cancer chemoresistance, and the immune-cold tumor microenvironment. The authors evaluated three relationship frameworks: direct suppression by mitochondria-derived signals, parallel emergence under shared selective pressures, and reverse causation driven by immune exclusion.
What was found
The abstract reports no numerical data or quantitative outcomes. It describes mechanistic pathways through which mitochondrial adaptations (including oxidative phosphorylation dependence, redox buffering, mitophagy, dynamics, and metabolite release like lactate, succinate, fumarate, 2-hydroxyglutarate, and adenosine) promote tumor survival and impair T-cell, macrophage, and dendritic-cell function, as well as context-dependent mitochondrial DNA-STING signaling.
Why it matters
The paper provides a conceptual framework for targeting the mitochondrial-immune interface to overcome chemoresistance and enhance responses to cancer immunotherapy, highlighting considerations for biomarker selection and combination treatment timing.
Limits
The work is a narrative review presenting mechanistic reasoning with no original empirical data, quantitative findings, or systematic search methodology. Human clinical evidence for the proposed translational combinations is not provided in the abstract.
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