Next-generation digital pathology-based strategy for qualitative and quantitative analyses of the lymphoid structure-associated immunological imprint. Shown is the flow chart of the Digital Immune Imaging to Clinical Outcome (DIICO) strategy on the basis of data sets derived from the next-generation tissue image cytometry. This includes the tissues under investigation, the lymphoid structures under investigation and their characteristics, the set of profiling markers, the data-derived variables accounting for the spatial organization and anatomical features, the cellular composition as well as the functional activity of ILS/ELS. Additionally, given is an overview of the statistical evaluation with the main focus on the clinical relevance. ILS, isolated lymphoid structure; ELS, ectopic lymphoid structure; GC, germinal center; AID, activation-induced cytidine deaminase; NT, non-tumorous tissue; CRC, colorectal cancer; CRCLM, colorectal cancer liver metastasis.