{
  "abstract": "Background Upregulation of various integrins in both tumors and stromal cells make them attractive targets for immunotherapeutic agents in cancer. The RGD (Arg-Gly-Asp)-binding integrin, αvβ6, is a cell-surface receptor exclusively expressed on epithelial cells. αvβ6 has previously been shown to be expressed at high levels in solid cancers and has been implicated to play a pro-tumorigenic role. However, αvβ6 protein surface-expression has not been comprehensively studied to determine its frequency and intensity of expression in different human tumor indications and healthy tissues.Methods Cancer and healthy tissues (FFPE) were collected from either commercial suppliers or UK biobanks. As many samples as possible were obtained covering a range of epithelial cancers, regardless of stage or grade. Written informed consent was obtained from all patients, and the study protocols were approved by NHS Research Ethics Committees.αvβ6 protein expression was evaluated using immunohistochemistry (IHC) on 5μm cut tissue sections. The staining was performed on the Ventana Discovery Ultra using an αvβ6 rabbit monoclonal primary antibody and its IgG isotype control with DAB detection. A standard immunostaining protocol was used for all samples. All images were taken with an AT2 Aperio panoramic slide scanner (Leica). Frequency of αvβ6 positive tumors was assessed by staining tissue microarrays (TMAs) and archival tissue blocks.αvβ6 gene expression was evaluated using OmicSoft Studio (OncoLand, V12.6) to obtain expression data of the β6 integrin across The Cancer Genome Atlas (TCGA).Results High expression of β6 integrin mRNA was found in a range of carcinomas. High expression intensity and a high prevalence of positively was observed by IHC in multiple epithelial cancers including pancreatic, head and neck, bladder, non-small cell lung, endometrial and cholangiocarcinoma. αvβ6 was absent, or expressed weakly, in most adult healthy tissue, with the exception of strong expression in the transitional epithelium of healthy bladder and moderate expression in stomach. Further, expression of αvβ6 was also observed in patient-matched primary and metastatic lesions.Conclusions These data provide a first comprehensive analysis of αvβ6 expression, confirming its presence in the majority of carcinomas, and absence in most healthy tissues. These data provide key information for indication selection for αvβ6 targeted therapies and healthy tissues that should be considered for on-target toxicity, and provides additional evidence for the important biological role that αvβ6 integrin plays during tumour development.Ethics Approval Studies were carried out with appropriate ethical approval and Home Office licence references 19/WS/0164, 23/PR/0221Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal",
  "authors": [
    {
      "affiliations": [
        "Accession Therapeutics LTD, Oxford, UK"
      ],
      "name": "Thomas A Webb"
    },
    {
      "affiliations": [
        "Accession Therapeutics, Oxford, UK"
      ],
      "name": "Rahul C Khanolkar"
    },
    {
      "affiliations": [
        "Accession Therapeutics, Oxford, UK"
      ],
      "name": "Alexander T Baker"
    },
    {
      "affiliations": [
        "Accession Therapeutics LTD, Oxford, UK"
      ],
      "name": "Bent K Jakobsen"
    },
    {
      "affiliations": [
        "Accession Therapeutics LTD, Oxford, UK"
      ],
      "name": "Alan Parker"
    },
    {
      "affiliations": [
        "Cardiff University, Cardiff, UK"
      ],
      "name": "Izhar Bagwan"
    },
    {
      "affiliations": [
        "Accession Therapeutics LTD, Oxford, UK"
      ],
      "name": "David Krige"
    },
    {
      "affiliations": [
        "Accession Therapeutics, Oxford, UK"
      ],
      "name": "Dave Cole"
    },
    {
      "affiliations": [
        "Accession Therapeutics, Oxford, UK"
      ],
      "name": "Andrew B Gerry"
    }
  ],
  "title": "700 αvβ6 integrin expression in carcinomas: a promising target for cancer therapy",
  "uid": "50671abf-f324-5750-99a2-3003cdde6b54"
}