Model showing the topographical organization of tumor and immune cells in DLBCLs with immune-deficient, DC-enriched, and Mac-enriched TIMEs. (Top left) DLBCLs with immune-deficient TIMEs are characterized by cells in tumor-rich (TR) CNTs. Individual cell neighborhoods furthest from blood vessels have very few immune cells compared with tumor cells and are organized as TR/ImP neighborhoods, consistent with immune exclusion. Individual cell neighborhoods closer to blood vessels are characterized by greater, but still a minor, number of immune cells compared to tumor cells and include greater numbers of myeloid and DCs than T cells organized as TR/MyR neighborhoods, suggestive of ongoing antigen sampling and limited T-cell stimulation. Regions nearest blood vessels show the highest numbers of immune cells relative to tumor cells. They include a variety of cell lineages organized as TR/BInf neighborhoods, consistent with extravasation of multiple immune cell types into the local microenvironment. (Top right) DLBCLs with DC-enriched TIMEs are characterized by cells organized as tumor-poor (TP) and TR CNTs. Uniquely to DLBCLs with DC-enriched TIMEs, regions nearest blood vessels show expanded numbers of T cells in TP/TCR neighborhoods and expanded numbers of DCs, CD4⁺ and CD8⁺ T cells in TP/DCR neighborhoods. Cells in TP/TCR and TP/DCR neighborhoods are enriched near blood vessels but also extend into the tumor parenchyma, suggestive of an active immune response. (Bottom left) DLBCLs with Mac-enriched TIMEs are characterized by cells organized as TP CNTs in addition to TR CNTs. Uniquely to DLBCLs with Mac-enriched TIMEs, regions close to and far from blood vessels show expanded numbers of T cells in TP/TCR neighborhoods and expanded numbers of CD163⁺ M2-like macrophages, IDO-1⁺ myeloid cells, CD8⁺ T cells, and PD-1⁺LAG-3⁺ exhausted T cells in the TP/MacR neighborhoods. In addition, there is lower HLA-DR expression in TP/ImP neighborhoods, suggestive of reduced immune stimulation. BV, blood vessel.