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Organ Transplantation Techniques and Outcomes / Immune Cells in Cancer · Journal article
Frontiers in Cellular and Infection Microbiology · August 10, 2026
Raises a question worth testing. It does not answer one.
This is a mechanistic review that synthesizes immunometabolic evidence on macrophage polarization and metabolic reprogramming in transplantation, proposing that targeting metabolic nodes (glycolysis vs. OXPHOS/FAO) could complement immunosuppression. The work frames macrophage metabolism as a potential therapeutic leverage point but presents no new empirical evidence, clinical outcomes data, or trials to support practice change.
Journal article. Transplant recipients; review covers mechanisms relevant to ischemia-reperfusion injury, acute and chronic rejection, fibrosis, and post-transplant malignancy..
M1 macrophages rely on aerobic glycolysis and secrete pro-inflammatory cytokines (IL-1β, IL-6, TNF-α); M2 macrophages depend on OXPHOS and FAO for anti-inflammatory and tissue-repair functions. Pyruvate kinase M2 promotes M1 polarization via HIF-1α-dependent inflammatory transcription; carnitine palmitoyltransferase 1A supports M2 polarization through FAO-driven OXPHOS. Emerging metabolic enzyme inhibitors (e.g., 2-deoxyglucose) attenuate chronic lung allograft dysfunction; macrophage-specific MEK1/2 ablation via CRISPR/Cas9 reprograms glycolysis to OXPHOS and ameliorates cardiac rejection.
Generalizability to human transplant populations and safety profile of proposed metabolic interventions not established.
This review identifies macrophage metabolic reprogramming as a mechanistic target for future therapeutic intervention in transplantation. Clinicians should note that while the theoretical framework is well-articulated, the evidence consists of preclinical and immunometabolic studies; clinical translation and safety/efficacy validation in humans remain pending.
This is a comprehensive mechanistic review synthesizing preclinical and immunometabolic evidence linking macrophage metabolism to transplant outcomes, proposing therapeutic targets but reporting no original experimental or clinical data.
This review identifies macrophage metabolic reprogramming as a mechanistic target for future therapeutic intervention in transplantation. Clinicians should note that while the theoretical framework is well-articulated, the evidence consists of preclinical and immunometabolic studies; clinical translation and safety/efficacy validation in humans remain pending.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Organ transplantation is the definitive treatment for end-stage organ failure, yet long-term graft survival remains substantially limited by ischemia-reperfusion injury (IRI), allograft rejection, and chronic graft dysfunction. Current immunosuppressive regimens have not fully exploited the metabolic plasticity of macrophages, which are central orchestrators of both innate and adaptive immune responses in transplanted organs. Macrophages display remarkable functional plasticity, classically defined by pro-inflammatory (M1)/anti-inflammatory (M2) polarization, and this dual capacity renders them uniquely impactful in transplanted organs. Accumulating immunometabolic evidence indicates that this plasticity is governed by dynamic metabolic reprogramming orchestrated by key metabolic nodes: M1 macrophages rely primarily on aerobic glycolysis and secrete proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α, whereas M2 macrophages depend on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to sustain anti-inflammatory and tissue-repair programs. For example, pyruvate kinase M2, a key glycolytic enzyme, promotes M1 polarization via glycolytic reprogramming and HIF-1α-dependent inflammatory gene transcription, whereas the carnitine palmitoyltransferase 1A, a rate-limiting enzyme in FAO, supports M2 polarization through FAO-driven OXPHOS. Core metabolic pathways encompass carbohydrate metabolism-glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway-alongside FAO and amino acid catabolism. These pathways are dynamically modulated by microenvironmental cues, such as hypoxia, lactate, and succinate, and in turn dictate macrophage phenotypic identity and effector function. In this review, we comprehensively review the molecular mechanisms underpinning macrophage metabolic reprogramming, from early IRI and acute rejection to chronic rejection, fibrosis, and post-transplant tumor recurrence, linking metabolism to alloimmunity and oncological risk. Emerging therapeutic strategies target macrophage metabolism, including metabolic enzyme inhibitors such as 2-deoxyglucose, which attenuates chronic lung allograft dysfunction, cell-based therapies, nanoparticles, and gene editing, for example macrophage-specific MEK1/2 ablation via CRISPR/Cas9, which reprograms glycolysis to OXPHOS and ameliorates cardiac rejection. Harnessing these metabolic nodes may complement current immunosuppression and improve graft survival, warranting future clinical evaluation.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.