Resistance-oriented immunometabolic circuits in laryngeal squamous cell carcinoma: glycolysis-lactate signaling, mitochondrial stress, and tumor-myeloid crosstalk.

Laryngeal squamous cell carcinoma (LSCC) remains clinically challenging because of immune escape and resistance to chemotherapy, radiotherapy, and immune checkpoint blockade. Although immunometabolism encompasses diverse nutrient, redox, and stromal pathways, LSCC-specific evidence is currently strongest for glycolysis/lactate metabolism, mitochondrial remodeling, oxidative stress adaptation, ferroptosis-related regulation, extracellular-vesicle-mediated macrophage remodeling, and checkpoint-associated T-cell dysfunction. This focused review therefore examines resistance-oriented immunometabolic circuits rather than providing an exhaustive catalogue of all metabolic pathways. We discuss how glycolytic activation and lactate accumulation may generate nutrient-competitive and acidic niches; how mitochondrial stress, ROS adaptation, and ferroptosis-related processes influence tumor survival; and how tumor-derived vesicles, TAMs, TILs, Tregs, pDCs, and emerging neutrophil/CAF-related signals shape immune escape. Underexplored axes, including lipid and amino-acid metabolism, glutamine dependence, arginine metabolism, tryptophan-IDO signaling, adenosine metabolism, hypoxia/HIF signaling, NK cells, MDSCs, endothelial cells, and broader stromal-immune interactions, are highlighted as evidence gaps requiring LSCC-specific validation. This review proposes a focused framework for biomarker development and rational combination therapy.