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

• Published in: Biochemistry and biophysics reports 2022-12, Vol.32, p.101365-101365, Article 101365
• Main Authors: D'Angelo, Alberto, Shibata, Kensuke, Tokunaga, Masayuki, Furutani-Seiki, Makoto, Bagby, Stefan
• Format: Article
• Language: English
• Subjects: Cancer organoids; Co-culture; Murine model; Pancreatic cancer; Peripheral blood mononuclear cell; Tumour microenvironment
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2022.101365

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. •Pancreatic cancer organoids co-cultured with PBMCs can establish an individualized ex-vivo model system to support T cell-based therapies.•Granzyme B intracellular staining showed increased tumour reactivity in T cells co-cultured with cancer organoids compared to healthy controls.•CD137 staining showed that the T cell responses induced by co-culture were specific to the cancer organoids.