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It also has the capacity to induce a systemic, anti\u2010tumor immune response, thus acting as an in situ vaccine. Although many studies characterize the immunogenicity of focal therapies by their released biochemical constituents, here we show that the biophysical context of the presentation of these immunogenic signals is vital to understanding downstream immune functions. Compared to thermal ablation or cryoablation, IRE generates similar numbers of exosome\u2010like particles (ELP, 50\u2013200\u2009nm) but significantly greater numbers of microparticles (MP, 200\u20131000\u2009nm) and large debris particles (LDP, 2\u20136\u2009\u03bcm) in both melanoma and pancreatic cancer cell lines. We show that LDPs contain antigen and tumor\u2010associated DNA, which dendritic cells (DCs) internalize in greater proportions from IRE\u2010treated cells compared to other treatments. For the submicron particles, we demonstrate both in vitro and in vivo that MPs induce greater T\u2010cell proliferation and differentiation compared to ELPs on a per\u2010particle basis. This novel biophysical analysis of the immunogenicity of IRE\u2010treated cancer cells opens a new avenue toward improving the systemic immune response to focal ablation\u2010based cancer immunotherapies via increasing cell fragmentation and particle generation.<\/jats:p>","DOI":"10.1002\/btm2.70102","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T06:10:39Z","timestamp":1766470239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cellular fragmentation underlies the immunogenicity of irreversible electroporation\u2010mediated tumor cell killing"],"prefix":"10.1002","volume":"11","author":[{"given":"Joseph R.","family":"Vallin","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering and Materials Science University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon 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