Preclinical models for cancer immunotherapy: a systematic review of ex vivo and in vitro platforms

Background Cancer immunotherapy (CI) has shown remarkable clinical results in solid tumors, highlighting the need for robust in vitro and ex vivo models to improve efficacy and elucidate mechanisms of resistance. In vitro and ex vivo models represent a critical tool to advance CI. We conducted a systematic review to: (1) map the use of preclinical models across cancer types, immune contexts, and immunotherapies, evaluating their degree of transferability and (2) provide a comprehensive dataset of studies employing these platforms to guide researchers. Methods Adhering to PRISMA 2020, we searched PubMed (2000–2025) for studies in vitro or ex vivo models of solid tumors tested in an immuno-oncology context. The main extracted domains included model type, immune-cell representation, type of immunotherapy assessed, and relative transferability (with culture setup, validation, and species recorded for contextual comparison). Extracted data were summarized into structured tables reported separately. Results We included 75 studies spanning six main experimental model types: patient-derived organoids (PDOs), 3D spheroid, 2D cell lines, Tumor tissue slices, Tumor-on-a-Chip, and other types across 23 cancer types with a prevalence of lung, breast and colorectal cancers. The main immune cell type used were T lymphocytes (i.e. TILs and CAR-T cells) followed by NK cells. Models investigated different immunotherapy regimens such as Immune Checkpoints inhibitors, particularly anti-PD-1/PD-L1 antibodies, followed by ACT such as CAR-T and NK cell-based therapies. While 2D models remain useful for initial screening, 3D spheroids and PDOs provide greater spatial and patient-derived context; tissue slices preserve native tumor architecture over short culture windows; and tumor-on-a-chip systems are particularly suited to modeling dynamic processes such as perfusion, gradients, and immune-cell trafficking. Conclusions We have generated a curated catalogue of models for CI that provides researchers with a valuable resource to advance experimental immunotherapy and preclinical testing.