Profiling Nascent Tumor Extracellular Vesicles via Metabolic Timestamping and Aptamer-Driven Specific Click Chemistry

EV levels and tumor volume. Proteome profiling of isolated nascent tEVs identified previously unknown upregulated vesicle proteins following immunotherapy, including key regulators of immune activation and suppression, suggesting that tumors orchestrate an intricate dual adaptive response through tEV secretion modulation to simultaneously elicit therapeutic sensitivity and resistance. Notably, among the upregulated proteins, we identified HSP70, whose enhanced presentation on tEVs promotes antitumor immunity and inhibits tumor growth. Thus, STAMP provides an effective gateway for studying EV dynamics with cell-origin accuracy and for identifying potential therapeutic targets based on EV transitions.