Generation of murine tumour-reactive T cells by co-culturing murine pancreatic cancer organoids and peripheral blood lymphocytes

Alberto D'Angelo, Kensuke Shibata, Masayuki Tokunaga, Makoto Furutani-Seiki, Stefan Bagby

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at a late stage and becomes resistant to several treatments. Significant clinical effects have been reported for cancer immunotherapies on a subset of patients diagnosed with epithelial cancers. Cancer organoid co-culture with autologous peripheral blood lymphocytes offers an innovative immunotherapeutic approach that is increasingly being tested, although there is a lack of cutting-edge platforms enabling the investigation of cancer-T cell interactions for individual patients. In this study, a pancreatic cancer organoid culture from a genetically engineered pancreatic cancer murine model was established and co-cultured with autologous peripheral blood lymphocytes to induce a tumour-specific T cell response to pancreatic cancer. Co-culturing autologous peripheral blood lymphocytes with cancer organoids can be an effective strategy to enrich tumour-reactive T cells from the peripheral blood of murine models; this approach could potentially be transferred to humans. Co-culture of peripheral blood lymphocytes and cancer organoids could provide an unbiased approach to evaluating the sensitivity of tumour cells to T cell-mediated priming on an individual patient level.

Original languageEnglish
Article number101365
JournalBiochemistry and Biophysics Reports
Volume32
Early online date9 Oct 2022
DOIs
Publication statusE-pub ahead of print - 9 Oct 2022

Keywords

  • Cancer organoids
  • Co-culture
  • Murine model
  • Pancreatic cancer
  • Peripheral blood mononuclear cell
  • Tumour microenvironment

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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