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Oncolytic peptide LTX-315 is known to elicit a strong antitumor immune response and durable immune memory. This study aimed to investigate whether LTX-315 could enhance nsPEF-induced antitumor immunity in liver cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Both cell assays and mouse models were used to evaluate the therapeutic efficacy of nsPEF, LTX-315, and combination therapy. Flow cytometry and immunofluorescence were performed to assess the tumor immune microenvironment. Co-culture models were established to evaluate the functional modulation of immune cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      nsPEF upregulated the programmed cell death 1 ligand 1 (PD-L1) expression in liver cancer cells, leading to CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell dysfunction. LTX-315 reduced the nsPEF-mediated elevated PD-L1 level and restored the cytotoxicity of CD8+ T cells. Furthermore, LTX-315 acted with nsPEF to induce enhanced immunogenic cell death for the activation of dendritic cells and CD8+ T cells. In addition, LTX-315 improved antigen processing and presentation in nsPEF-treated liver cancer cells. Notably, the combination of nsPEF and LTX-315 achieved durable tumor control and prolonged survival of the tumor-bearing mice, by promoting the migration of dendritic cells to tumor-draining lymph nodes, the infiltration of immune cells within the tumor and potential immune memory to prevent tumor metastasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LTX-315 functions as an immune stimulant to improve the antitumor efficacy of nsPEF. The combination of nsPEF and LTX-315 represents a promising interventional immunotherapy strategy for liver cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>LTX-315; Antitumor immune response; nsPEF; Liver cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012438","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T05:20:19Z","timestamp":1769664019000},"page":"e012438","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Oncolytic peptide LTX-315 targets PD-L1 to improve antitumor immune response of nanosecond pulse electric field in liver cancer"],"prefix":"10.1136","volume":"14","author":[{"given":"Kun","family":"Ji","sequence":"first","affiliation":[{"name":"Hepatobiliary and Pancreatic Interventional Treatment Center, Division of 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