Figure 1.
IMC analysis of DLBCL TME identifies heterogeneity of immune infiltration and cellular subtypes. (A) The complete single-cell network uniform manifold approximation and projection (UMAP) depicts the manifold approximation for each cell and shows the lineage marker intensity correspondence to each manifold. UMAP (left) depicts the identified tumor, CD4, CD8, TREG, macrophage, and endothelial components generated by PhenoGraph clustering. Each PhenoGraph subpopulation is denoted with a color organized by TME compartments related to the primary lineage marker. The adjacent UMAP (right) depicts the primary lineage marker (min/max) intensity of each major phenotype. The corresponding heatmap depicts the min/max normalized expression intensity summarized by major cell components. (B) Of the 39.5% of cells composing the TME, the composition was dominated by CD4, CD8, and macrophages, which make up 92.3% of the immune microenvironment. In a multivariate beta model adjusted for each Chapuy signature class, cell-of-origin, and high IPI (≥ 3), CD4 T cell-relative TME proportion was 2.88 (95% CI, 1.26-6.57; P = .012) times increased among cases in C4 coordinate signature compared with cases not in C4. CD8 T-cell TME proportion was 1.96 (95% CI, 1.11-3.48; P = .02) times increased among C2 cases compared with other signatures, whereas TREG TME proportions were 0.40 (95% CI, 0.19-0.86; P = .019) times that of those not in C2. These data suggest, holding other terms as constant, that there is heterogeneity of TME abundances associated with molecular signatures. (C) Left: Initial pathologist review revealed various degrees of immune infiltrate in DLBCL. Pseudo-colored images representative of cases with low (top), medium (middle), and high (bottom) degree of immune infiltrate. Right: Cases ranked in order of absolute proportion of immune cells (9.42%-90.14%). See Supplemental Figure 7 for all cases. (D) Analysis of the TME composition showed marked heterogeneity in the distribution of CD4, CD8, TREG, and macrophages across cases, such that the proportion of CD4 increases with the increasing proportion of immune infiltrate, but the proportion of macrophages decreases with the increasing proportion of immune infiltrate. (E) Negative correlation between the proportion of CD4 T cells and that of macrophages. The x-axis denotes CD4 T-helper case proportions and the y-axis denotes the macrophage case proportions.

IMC analysis of DLBCL TME identifies heterogeneity of immune infiltration and cellular subtypes. (A) The complete single-cell network uniform manifold approximation and projection (UMAP) depicts the manifold approximation for each cell and shows the lineage marker intensity correspondence to each manifold. UMAP (left) depicts the identified tumor, CD4, CD8, TREG, macrophage, and endothelial components generated by PhenoGraph clustering. Each PhenoGraph subpopulation is denoted with a color organized by TME compartments related to the primary lineage marker. The adjacent UMAP (right) depicts the primary lineage marker (min/max) intensity of each major phenotype. The corresponding heatmap depicts the min/max normalized expression intensity summarized by major cell components. (B) Of the 39.5% of cells composing the TME, the composition was dominated by CD4, CD8, and macrophages, which make up 92.3% of the immune microenvironment. In a multivariate beta model adjusted for each Chapuy signature class, cell-of-origin, and high IPI (≥ 3), CD4 T cell-relative TME proportion was 2.88 (95% CI, 1.26-6.57; P = .012) times increased among cases in C4 coordinate signature compared with cases not in C4. CD8 T-cell TME proportion was 1.96 (95% CI, 1.11-3.48; P = .02) times increased among C2 cases compared with other signatures, whereas TREG TME proportions were 0.40 (95% CI, 0.19-0.86; P = .019) times that of those not in C2. These data suggest, holding other terms as constant, that there is heterogeneity of TME abundances associated with molecular signatures. (C) Left: Initial pathologist review revealed various degrees of immune infiltrate in DLBCL. Pseudo-colored images representative of cases with low (top), medium (middle), and high (bottom) degree of immune infiltrate. Right: Cases ranked in order of absolute proportion of immune cells (9.42%-90.14%). See Supplemental Figure 7 for all cases. (D) Analysis of the TME composition showed marked heterogeneity in the distribution of CD4, CD8, TREG, and macrophages across cases, such that the proportion of CD4 increases with the increasing proportion of immune infiltrate, but the proportion of macrophages decreases with the increasing proportion of immune infiltrate. (E) Negative correlation between the proportion of CD4 T cells and that of macrophages. The x-axis denotes CD4 T-helper case proportions and the y-axis denotes the macrophage case proportions.

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