Figure 3.

Application of organoids in Cancer Immunotherapy. The TME can be generated in PDOs by two types of approaches: the reconstituted TME (Upper panel, pink color) and the native TME (Below panel, blue color). In the reconstituted system, PDOs were exclusively generated from tumor cells after physical or enzymatical digestion. Organoids are cultured in extracellular matrix dome (Matrigel or BME (Basement Membrane Extract)). Organoids were co-cultured with autologous PBMC isolated from peripheral blood, lymph node, or from tumor. In native TME model, tumors were minced or enzymatically digested, then filtered to obtain appropriately sized fragments, embedded into collagen-based extracellular matrix with medium in the top. Alternatively, in air–liquid interface (ALI) culture, native tumor fragments are embedded in collagen matrix on the top of a transwell insert exposed to air with culture medium below it. Numerous downstream applications of organoids in immunotherapy followed by systemic functional and quantitative analysis are summarized in the right panel. It allows the interaction between immune cells and tumor cells to be defined, in order to identify and predict the clinically relevant immunotherapy strategy for patients. Abbreviations: CAR, chimeric antigen receptor; NK, Natural killer; ICI, immune checkpoint inhibitors, CTLA4, cytotoxic T-lymphocyte associated protein4; PD-1, programmed cell death-1; LAG-3, Lymphocyte-activation gene 3; TIM-3, T-cell immunoglobulin and mucin containing protein-3. This figure was created with BioRender.com (accessed on 14 March 2023).