Figure 3.
Figure 3. Decreased MHC-II gene expression and immune checkpoint deregulation cooperate with ABC-DLBCL genetic hallmarks to promote immune evasion. (A) Comparative gene expression levels of the MHC-II transactivator CIITA in GFP+/YFP+ reporter murine B cells from control or tumoral spleens (left) and human DLBCL (right, GSE10846). (B) Heat map of gene expression levels for MHC-II genes (KEGG pathway mmu04612) in GFP+/YFP+ reporter murine B cells from control or tumoral spleens. (C) Representative FACS histograms and comparative levels of surface PD-L1 in GFP+/YFP+ reporter murine B cells (left), and PD-L1 gene expression levels in human DLBCL (right, GSE10846). (D) Pie charts showing average percentages (n = 4 animals) of different immune cells in the control or tumoral spleens. (E) Comparative percentages of different T-cell populations in the control or tumoral spleens of indicated mice. (F-G) Multidimensional depiction by t-SNE of surface marker levels in aggregated total CD8+ T cells (dots) from control or tumoral spleens (n = 4 animals). Expression by FACS of coinhibitory and exhaustion markers (F) or activation and differentiation markers (G) were overlaid onto the overall t-SNE maps. Interpretation of the overall phenotype for each CD8+ T cell is color coded and annotated as nonexhausted (nEx; PD-1negLAG-3neg2B4neg), exhausted (Ex; PD-1hi), hyperexhausted cells that coexpress multiple inhibitory receptors besides PD-1 (hEx), naive (N; CD44lowCD62L+), central memory (CM; CD44highCD62L+), and effector or effector memory (E/EM; CD44highCD62Lneg). Percentages indicate average abundance of CD8+ T cells with the different exhaustion/differentiation phenotypes in YC control spleens or BIC/pBIC lymphomas.

Decreased MHC-II gene expression and immune checkpoint deregulation cooperate with ABC-DLBCL genetic hallmarks to promote immune evasion. (A) Comparative gene expression levels of the MHC-II transactivator CIITA in GFP+/YFP+ reporter murine B cells from control or tumoral spleens (left) and human DLBCL (right, GSE10846). (B) Heat map of gene expression levels for MHC-II genes (KEGG pathway mmu04612) in GFP+/YFP+ reporter murine B cells from control or tumoral spleens. (C) Representative FACS histograms and comparative levels of surface PD-L1 in GFP+/YFP+ reporter murine B cells (left), and PD-L1 gene expression levels in human DLBCL (right, GSE10846). (D) Pie charts showing average percentages (n = 4 animals) of different immune cells in the control or tumoral spleens. (E) Comparative percentages of different T-cell populations in the control or tumoral spleens of indicated mice. (F-G) Multidimensional depiction by t-SNE of surface marker levels in aggregated total CD8+ T cells (dots) from control or tumoral spleens (n = 4 animals). Expression by FACS of coinhibitory and exhaustion markers (F) or activation and differentiation markers (G) were overlaid onto the overall t-SNE maps. Interpretation of the overall phenotype for each CD8+ T cell is color coded and annotated as nonexhausted (nEx; PD-1negLAG-3neg2B4neg), exhausted (Ex; PD-1hi), hyperexhausted cells that coexpress multiple inhibitory receptors besides PD-1 (hEx), naive (N; CD44lowCD62L+), central memory (CM; CD44highCD62L+), and effector or effector memory (E/EM; CD44highCD62Lneg). Percentages indicate average abundance of CD8+ T cells with the different exhaustion/differentiation phenotypes in YC control spleens or BIC/pBIC lymphomas.

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