Immune-metabolic profiling of triple-negative breast cancer during neoadjuvant chemotherapy.

This multi-omics study investigated immune and metabolic determinants of neoadjuvant chemotherapy (NAC) response in triple-negative breast cancer. Analyzing samples from 32 patients, responders exhibited systemic and intratumoral expansion of metabolically active, functionally competent immune cells, including effector memory T cells and activated dendritic cells with enhanced oxidative phosphorylation. Non-responders displayed immune exhaustion and metabolic suppression, with enriched terminally differentiated T cells and senescent NK cells. Transcriptomic and spatial analyses revealed that non-responder tumors were dominated by hypoxia, driving fatty acid oxidation and lymphocyte dysfunction. These findings demonstrate that pre-treatment immune-metabolic fitness in T and B cells is strongly associated with chemosensitivity, offering a promising avenue for predictive biomarker development.