Patient-derived models of tumor-immune cell interactions.

Novel therapeutic approaches highlight the need for advanced ex vivo cell culture models that more closely resemble the physiological and genetic properties of the primary tumor. Patient-derived models could serve as an attractive strategy to investigate the crosstalk between cancer cells and its microenvironment and to test potential therapeutic targets, paving the way for precision oncology. In this chapter, we provide a detailed step-by-step protocol for enabling a direct co-culture system of patient-derived colorectal cancer (CRC) organoids with autologous tumor-infiltrating lymphocytes (TILs). The present protocol provides a methodology to gain direct access to the apical side of the epithelial cells forming the organoids. This method can be used to investigate patient-specific cell-to-cell interactions, T cell functionality and efficacy and provides a robust platform to validate potential immunogenic neoantigens.