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Background <p>PD-L1 immunotherapy plays a crucial role in cancer treatment, but PD-L1 peptide vaccines have low immunogenicity. 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.</p> Methods <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–MS/MS were used to explore putative mechanisms.</p> Results <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-γ–linked pathways, and an exploratory docking screen nominated candidate receptors/pathways potentially connecting the adjuvant motif to innate sensing.</p> Conclusions <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.</p> Graphical abstract <p></p>

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A SARS-CoV-2 spike-derived adjuvant peptide boosts IL-17/IFN-γ immunity and improves anti-PD-L1 therapy against melanoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月27日

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  • Chia-Hung Chen,
  • Tzu-Han Weng,
  • Ta-Wei Kuo,
  • Kai-Yao Huang,
  • Yu-Chi Chen,
  • Hsiao-Hsuan Huang,
  • Hui-Ju Kao,
  • Chen-Lin Yu,
  • Chen-Chen Huang,
  • Shun-Long Weng,
  • Kuang-Wen Liao

摘要

Background

PD-L1 immunotherapy plays a crucial role in cancer treatment, but PD-L1 peptide vaccines have low immunogenicity. 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.

Methods

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–MS/MS were used to explore putative mechanisms.

Results

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-γ–linked pathways, and an exploratory docking screen nominated candidate receptors/pathways potentially connecting the adjuvant motif to innate sensing.

Conclusions

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.

Graphical abstract