PDAC tumor Immune system escape architecture: Analysis of transcriptomics of mechanisms that TME is tackling immune system in Pancreatic Ductal Adenocarcinoma Tumors

Pancreatic ductal adenocarcinoma (PDAC) evolves within a complex tumor microenvironment (TME) that promotes immune evasion and stromal reprogramming characterized by heterogeneous clonal architecture and frequent resistance to apoptosis [1,2,12]. Here, we performed analysis on single-cell RNA sequencing data from 79,409 cells isolated from the pancreas of PDAC patients to dissect intra-tumoral heterogeneity, mechanisms that tumor creates TME and identify anti-apoptotic programs. To dissect the cellular heterogeneity and the molecular hallmarks of PDAC progression, we established a single-cell transcriptomic framework integrating quality-controlled data across tumor and stromal compartments [3,4,10]. After rigorous filtering to remove potential doublets and cells with excessive mitochondrial transcript content (>30%), we generated a refined map of the PDAC cellular ecosystem [5–7]. Dimensionality reduction revealed distinct transcriptional programs, with principal component analysis (PCA) capturing key axes of heterogeneity driven by highly variable genes across clusters [8,9]. These data enabled functional annotation of epithelial, immune, and stromal subpopulations and highlighted dominant patterns of regulatory T cells, activated fibroblasts, and macrophage polarization toward tumor-supportive phenotypes [2,11,12]. Collectively, our transcriptomic profiling delineates the architectural and functional complexity of the PDAC TME and reveals molecular adaptations that progressively establish tumor-permissive conditions [1,3,4].