Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids
By K. Dijkstra, C. Cattaneo, F. Weeber, M. Chalabi, J. van de Haar, Lorenzo F. Fanchi, M. Slagter, D. L. van der Velden, S. Kaing, S. Kelderman and 14 more. Cell, 2018
973 citations recorded by the source corpus.
Summary Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer – T cell interactions for individual patients, and understand determinants of responsiveness, are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses for epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich for tumor-reactive T cells from peripheral blood of patients with mismatch repair deficient colorectal cancer and non-small cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/272ad6ae60e87cf885e424dc52006920382b125a
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Citations in the corpus
- Neoantigens: promising targets for cancer therapy (2023, background): “In addition, coculturing autologous PBMCs with tumor organoids produced personalized tumor-reactive CD8 T lymphocytes that significantly reduced the growth of tumors.(405,510) Although further improvements are required to conserve TME, including myeloid and stromal components, the organoid model may”
- Organoid modeling of the tumor immune microenvironment (2018, methodology): “…cell types besides T cells, including macrophages, B, and NK cells, versus reconstitution of clonally expanded or TCR-engineered TIL populations added to tumor cells (Feder-Mengus et al., 2008; Hirt et al., 2014; Dijkstra et al., 2018; Feldman et al., 2015; Forget et al., 2017; Tran et al., 2016).”
- Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients (2019, methodology): “Culture methods that at least partially retain the patient tumor microenvironment in vitro might provide a platform to overcome this hurdle and offer valuable insight into the multilevel interaction of 5-FU and oxaliplatin (23, 28).”