{
  "abstract": "Background Immunotherapy by immune checkpoint blockade (ICB) has revolutionised the treatment of cancers such as Melanoma and non-small cell lung cancer. However, many patients do not respond to ICB whilst some cancers are largely resistant. ICB is also characterised by immune related adverse events which limits the ability to combine ICB with other immunotherapies. Studies identifying predictive biomarkers and factors influencing the efficacy of ICB have indicated that the patient gut microbiome plays an important role in ICB response by priming anti-tumour immunity. The gut microbiome may mediate this effect through numerous mechanisms including the expression of immunogenic metabolites.Methods Dendritic cells and myeloid derived suppressor cells were generated in vitro prior to stimulation with butyrate. The ability of these cells to modulate autologous CD8+ T-cell function was measured using ELISA and flow cytometry. The ability of butyrate, +/- other immunogenic metabolites, to alter the polyfunctional activation of CD8+ T-cells from healthy donors and melanoma patients was determined using flow cytometry. The presence of metabolites in the plasma of melanoma patients was also determined and associated with markers of T-cell activation.Results The short chain fatty acid butyrate is produced by gut resident bacteria associated with ICB responses, but its role in T-cell function is incompletely understood. We have found that butyrate alters the function of dendritic cells matured by innate immune ligands used as cancer immunotherapies. Butyrate also enhances the expression of Interferon-γ from CD8+ T-cells upon TCR ligation, alters the expression of tumour necrosis factor super family receptors and maintains the responsiveness of CD8+ T-cells with exhausted phenotypes. Butyrate demonstrated an ability to alter the expression of immune checkpoints on T-cells. Finally, butyrate combined with other immunogenic metabolites to further modulate T-cell function.Conclusions Collectively these data provide evidence supporting metabolites such as butyrate as adjunct therapies for ICB immunotherapy.",
  "authors": [
    {
      "affiliations": [
        "St Georges University of London, London, UK"
      ],
      "name": "Peter L Smith"
    },
    {
      "affiliations": [
        "St Georges University of London, London, UK"
      ],
      "name": "Angus Dalgleish"
    }
  ],
  "title": "1133 The short chain fatty acid butyrate modulates myeloid cell activation, CD8+ T-cell function and checkpoint expression",
  "uid": "acc0daa4-c560-513e-8fcf-52950dd73530"
}