(A) Left, Z-score clustermaps based on median and mean cell counts in DhE, non-DhE, and MYC/BCL2 double-hit lymphoma (DHL) cases, respectively; right, representative Uniform Manifold Approximation and Projection (UMAP) plots generated from single-cell intensities for six markers (CD20, CD3, CD68, CD56, PD-1, and PD-L1) in two LymphGen-unclassified cases. UMAP legends of CD20+, CD3+, CD56+, and CD68+ meant single positive. (B) Left, a box plot to show the distribution and significant differences in absolute cell counts of immunophenotypes between DhE/DH and non-DhE cases by two-sided Mann-Whitney U test. Asterisks mark significant differences. *: P ≤ 0.05, **: P ≤ 0.01, ***: P ≤ 0.001. Significant differences between DhE and non-DhE cases are also marked by asterisks in the median Z-score clustermap above. Right, three scatter plots showing that DhE and high Ki-67 scores were significantly associated with lower T cell percentages in overall DLBCL-NOS and that DhE was associated with lower PD-1 expression in T cells in GCB-DLBCL-NOS cases. P values are by 2-tailed unpaired t test (also significant by Mann-Whitney U test). Each dot represents one patient. (C) In DhE-DLBCL-NOS and MYC/BCL2-DHL cases, FN1-positive and FN1-high expression in the tumor microenvironment were associated with significantly poorer overall survival (OS) and progression-free survival (PFS), respectively. In DhE-DLBCL-NOS, deficiency in T cell and NK cell infiltration was associated with significantly poorer OS.