Using small tumor samples from patients with non-small-cell lung or mismatch repair-deficient colorectal cancer, Dijkstra and Cattaneo et al. created tumor organoids and co-cultured them with autologous PBMCs in order to enrich for tumor-reactive T cells. Tumor-specific CD107a+ or IFNγ+ CD8+ T cells were induced in ~50% of the co-cultures and these cells killed the epithelial tumor organoids. Detection of CD4+ T cell responses was low and confounded by reactivity to the murine matrix in which organoids were cultured. This tumor organoid platform may be used to assess tumor sensitivity and resistance to T cell killing or to provide T cell products on an individual basis.
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 to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich 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 by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.