Decoding the immune–tumor synapse for data-driven design of next-generation immunotherapies

The immunological synapse (IS) formed between cytotoxic CD8⁺ T lymphocytes (CTLs) and tumor cells represents the critical interface where many immunotherapies act, including therapeutic antibodies and chimeric antigen receptor immunotherapy. However, detailed characterization of the CTL-tumor IS has remained limited, primarily due to the transient and dynamic nature of this structure. Recent advances in proteomics, transcriptomics, high-throughput imaging, and machine learning are now enabling more precise investigation of this complex cell-cell interaction. This review highlights how emerging technologies have advanced our understanding of the CTL-tumor IS, outlines their potential to inform next-generation immunotherapies, and proposes future directions for technological innovation.