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A potent peptide derived from the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant adjuvant effect, which may increase the immunogenicity of the PD-L1 peptide. This study evaluates whether the PD-L1-SARS peptide enhances PD-L1 immunotherapy and analyzes its potential synergistic effects with anti-PD-L1 antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo experiments compared prevention, therapy, and combination therapy using PD-L1 versus PD-L1-SARS peptides in mice. Cytokine multiplex arrays, ELISpot, and IHC were used to evaluate adjuvant effects. Molecular docking (hypothesis-generating), RNA-seq, and LC\u2013MS\/MS were used to explore putative mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The PD-L1-SARS peptide enhanced the Th1 immune response and increased CD8 and Th17 cell infiltration, effectively inhibiting tumor growth and liver metastasis. Additionally, it promoted M1 macrophage polarization and improved anti-PD-L1 antibody efficacy. Proteomics and bioinformatic analyses were consistent with IFN-\u03b3\u2013linked pathways, and an exploratory docking screen nominated candidate receptors\/pathways potentially connecting the adjuvant motif to innate sensing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Embedding a SARS-derived adjuvant-like motif within a PD-L1 peptide vaccine and delivering it in situ may re-condition the tumor microenvironment toward an immune-activating, Th1\/Th17-biased state and complement PD-L1 blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-025-01384-2","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T07:15:32Z","timestamp":1766819732000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A SARS-CoV-2 spike-derived adjuvant peptide boosts IL-17\/IFN-\u03b3 immunity and improves anti-PD-L1 therapy against melanoma"],"prefix":"10.1186","volume":"31","author":[{"given":"Chia-Hung","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Han","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta-Wei","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Yao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Hsuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ju","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Lin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Chen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Long","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Wen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"issue":"1","key":"1384_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01674-3","volume":"8","author":"T Fan","year":"2023","unstructured":"Fan T, Zhang M, Yang J, Zhu Z, Cao W, Dong C. 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