Data from Senescent Cell–Derived Extracellular Vesicles Inhibit Cancer Recurrence by Coordinating Immune Surveillance

• DOI: 10.1158/0008-5472.c.7700617
• Publication Date: 2025-03-03T08:43:11Z
• Authors: Tahereh Ziglari; Nicholas L. Calistri; Jennifer M. Finan; Daniel S. Derrick; Ernesto S. Nakayasu; Meagan C. Burnet; Jennifer E. Kyle; Matthew Hoare; Laura M. Heiser; Ferdinando Pucci
• Keywords: Extracellular Vesicles; Immune surveillance

<div>Abstract<p>Senescence is a nonproliferative survival state that cancer cells can enter to escape therapy. In addition soluble factors, senescence secrete extracellular vesicles (EV), which are important mediators of intercellular communication. To explore the role senescent cell (SC)–derived EVs (senEV) in inflammatory responses senescence, we developed an engraftment-based model wild-type mice and genetically blocked senEV release <i>in vivo</i>, without significantly affecting mediators. SenEVs were both necessary sufficient trigger immune-mediated clearance SCs, thereby suppressing tumor growth. absence senEVs, recruitment MHC-II<sup>+</sup> antigen-presenting (APC) microenvironment was markedly impaired. Blocking redirected primary target SC signaling from APCs neutrophils. Comprehensive transcriptional proteomic analyses identified six ligands specific highlighting their promoting APC–T adhesion synapse formation. activated CCR2<sup>+</sup>CD4<sup>+</sup> T<sub>H17</sub> cells, seemed inhibit B-cell activation, CD4<sup>+</sup> T essential for preventing recurrence. These findings suggest senEVs complement activity secreted by recruiting activating distinct immune subsets, enhancing efficient SCs. conclusions may have implications not only recurrence but also understanding during <i>de novo</i> carcinogenesis. Consequently, this work could inform development early detection strategies based on biology cellular senescence.</p><p><b>Significance:</b> Chemotherapy-treated response suppress recurrence.</p><p><i><a href="https://aacrjournals.org/cancerresearch/article-abstract/doi/10.1158/0008-5472.CAN-24-4775" target="_blank">See related commentary Almeida Melo, p. 833</a></i></p></div>