Journal: Cellular Oncology (Dordrecht, Netherlands)
Article Title: Platelets in the tumor microenvironment: potential mediators of immune exclusion and resistance to immune checkpoint inhibitor therapy
doi: 10.1007/s13402-025-01129-7
Figure Lengend Snippet: Platelet-Driven CAF Activation and ECM Barriers in the Tumor Microenvironment. A. Expression levels of TGFB1 and PDGFB were assessed using pan-tissue single-cell RNA-sequencing data from the Human Protein Atlas. Normalized counts (nCPM) were aggregated at the cell-type level. Among all surveyed human cell types, platelets showed the highest expression of TGFB1 and were among the top expressors of PDGFB, highlighting their distinct capacity as a concentrated source of these exclusion-related factors. B. Activated platelets engage CAFs via CLEC-2–podoplanin interaction and release TGF-β, PDGF, and SDF-1, inducing fibroblast, epithelial cell, and MSC differentiation into CAFs. MSCs activate platelets via PAF, forming a feedback loop. CAFs (α-SMA/FAP + ) remodel the ECM and promote desmoplasia, creating a barrier to T cell infiltration and sustaining immune suppression in the TME. Abbreviations: CAF: Cancer-Associated Fibroblast, CLEC-2: C-type Lectin-like Receptor 2, PDPN: Podoplanin, TGF-β: Transforming Growth Factor Beta, PDGF: Platelet-Derived Growth Factor, SDF-1: Stromal Cell-Derived Factor 1, MSC: Mesenchymal Stem Cell, PAF: Platelet-Activating Factor, α-SMA: Alpha-Smooth Muscle Actin, FAP: Fibroblast Activation Protein, ECM: Extracellular Matrix, TME: Tumor Microenvironment
Article Snippet: Our analysis of pan-tissue single-cell transcriptomic data from the Human Protein Atlas identifies platelets as a dominant cellular source of TGF-β and among the highest expressors of PDGFB across human cell types (Fig. A), providing a strong molecular basis for their impact on CAF activation and differentiation.
Techniques: Activation Assay, Expressing, RNA Sequencing, Derivative Assay