Core Viewpoint - The study reveals a signaling axis involving visceral adipose tissue-derived extracellular vesicles (VAT-EV) that promotes pancreatic cancer development and resistance to immune checkpoint blockade therapy in obese patients, suggesting potential new therapeutic strategies for obesity-related cancers [4][7]. Group 1: Research Findings - The research identifies that VAT-EV from obese patients facilitates communication with pancreatic ductal adenocarcinoma (PDAC) tissues [4]. - PDAC cells can internalize VAT-EV, leading to the stabilization of ribonuclease Rnaset2b and the production of free pseudouridine [4][5]. - Pseudouridine activates mast cells by increasing reactive oxygen species (ROS) and reducing H3K27me3 modifications, creating an immunosuppressive tumor microenvironment that promotes cancer progression [4][5]. Group 2: Implications for Therapy - Targeting the VAT-EV-CTSA-pseudouridine-mast cell signaling pathway could enhance the efficacy of immune checkpoint blockade therapy for PDAC [5][7]. - The study provides hope for developing new treatment strategies for obesity-related cancers by elucidating the molecular mechanisms linking obesity and cancer [7].