Figure 3.
MHC class II signaling downregulation mediated immune evasion at postchemotherapy relapse. (A) Overview of paired diagnostic-relapse (Dx-Rel) patients with pAML in distinct subtypes. Pie charts indicate clinical blast count, and the time of sample collections relative to diagnosis. (B) UMAP display of 8 paired diagnostic and relapse pAML samples across distinct subtypes based on top 25 000 variable peaks. Shape and color represent relapse state. (C) Bar plot illustrating the shift of cellular composition from diagnosis to relapse in distinct subtypes. (D) Top 10 enriched GO terms of differentially accessible regions in HSC/MPP-like cells between paired diagnostic and relapse samples. Color indicates the significance of enrichment. (E) Gene score of MHC class II molecules in HSC/MPP-like cells between diagnostic and relapse samples across distinct subtypes. ∗P < .05; ∗∗P < .01, Wilcoxon rank-sum test. (F) Gene score of the positive regulators of MHC class II genes in HSC/MPP-like cells between diagnostic and relapse samples across distinct subtypes. ∗P < .05; ∗∗P < .01, Wilcoxon rank-sum test. (G) Genome browser tracks illustrating chromatin accessibility for CIITA (a positive regulator for MHC class II genes) and RREB1 (a negative regulator for MHC class II genes) in diagnostic and relapse samples across distinct pAML subtypes. Each track shows merged pseudo-bulk ATAC-seq signal. (H) Gene score of MHC class II genes across various cell types between relapse and diagnosis samples. ∗P < .05, Wilcoxon rank-sum test. (I) Scatter plot showing the Spearman correlation (with a 95% confidence interval for the regression line) between the gene score of MHC class II genes and the clone size in pAML2 at relapse. The upper left corner displays the Spearman correlation coefficient (R) and the P value. (J) Gene score of MHC class II genes compared between relapse and nonrelapse groups in different pAML subtypes. Wilcoxon rank-sum test. (K) Flow cytometry was used to assess T-cell activation by measuring the percentage of CD4+ T cells positive for activation marker CD69. CD4+ T cells were cocultured with KG-1 cells for 72 hours, which had been preincubated with either anti–HLA-DR, -DP, -DQ blocking antibodies (KG1 + T cell + block) or an isotype control antibody (KG1 + T cell + Iso). Data are gated on live CD4+ T cells. Three independent experiments are performed. (L) Box plot showing percentage of CD69+ T cells in CD4+ T-cell population across different experimental conditions. CD4+ T cells were either cultured in medium alone (T cell + Medium) or coculturing with KG-1 cells (KG1 + T cell + Iso, KG1 + T cell + Block) for 72 hours. ∗∗P < .01; ∗∗∗P < .001, Wilcoxon rank-sum test. CDP, common dendritic cell progenitor; CFSE, carboxyfluorescein succinimidyl ester; Dx, diagnostic; EBM, eosinophil/basophil/mast cell; GMP, granulocyte/macrophage progenitor; LMPP, lymphoid-primed multipotential progenitor; MDP, monocyte-dendritic cell progenitor; MEP, megakaryocyte/erythroid progenitor; MLP, multilymphoid progenitor; NeP, neutrophil progenitor; NK, natural killer cell; Pre-B, precursor B cell; Pro-B, progenitor B cell; Rel, relapse.

MHC class II signaling downregulation mediated immune evasion at postchemotherapy relapse. (A) Overview of paired diagnostic-relapse (Dx-Rel) patients with pAML in distinct subtypes. Pie charts indicate clinical blast count, and the time of sample collections relative to diagnosis. (B) UMAP display of 8 paired diagnostic and relapse pAML samples across distinct subtypes based on top 25 000 variable peaks. Shape and color represent relapse state. (C) Bar plot illustrating the shift of cellular composition from diagnosis to relapse in distinct subtypes. (D) Top 10 enriched GO terms of differentially accessible regions in HSC/MPP-like cells between paired diagnostic and relapse samples. Color indicates the significance of enrichment. (E) Gene score of MHC class II molecules in HSC/MPP-like cells between diagnostic and relapse samples across distinct subtypes. ∗P < .05; ∗∗P < .01, Wilcoxon rank-sum test. (F) Gene score of the positive regulators of MHC class II genes in HSC/MPP-like cells between diagnostic and relapse samples across distinct subtypes. ∗P < .05; ∗∗P < .01, Wilcoxon rank-sum test. (G) Genome browser tracks illustrating chromatin accessibility for CIITA (a positive regulator for MHC class II genes) and RREB1 (a negative regulator for MHC class II genes) in diagnostic and relapse samples across distinct pAML subtypes. Each track shows merged pseudo-bulk ATAC-seq signal. (H) Gene score of MHC class II genes across various cell types between relapse and diagnosis samples. ∗P < .05, Wilcoxon rank-sum test. (I) Scatter plot showing the Spearman correlation (with a 95% confidence interval for the regression line) between the gene score of MHC class II genes and the clone size in pAML2 at relapse. The upper left corner displays the Spearman correlation coefficient (R) and the P value. (J) Gene score of MHC class II genes compared between relapse and nonrelapse groups in different pAML subtypes. Wilcoxon rank-sum test. (K) Flow cytometry was used to assess T-cell activation by measuring the percentage of CD4+ T cells positive for activation marker CD69. CD4+ T cells were cocultured with KG-1 cells for 72 hours, which had been preincubated with either anti–HLA-DR, -DP, -DQ blocking antibodies (KG1 + T cell + block) or an isotype control antibody (KG1 + T cell + Iso). Data are gated on live CD4+ T cells. Three independent experiments are performed. (L) Box plot showing percentage of CD69+ T cells in CD4+ T-cell population across different experimental conditions. CD4+ T cells were either cultured in medium alone (T cell + Medium) or coculturing with KG-1 cells (KG1 + T cell + Iso, KG1 + T cell + Block) for 72 hours. ∗∗P < .01; ∗∗∗P < .001, Wilcoxon rank-sum test. CDP, common dendritic cell progenitor; CFSE, carboxyfluorescein succinimidyl ester; Dx, diagnostic; EBM, eosinophil/basophil/mast cell; GMP, granulocyte/macrophage progenitor; LMPP, lymphoid-primed multipotential progenitor; MDP, monocyte-dendritic cell progenitor; MEP, megakaryocyte/erythroid progenitor; MLP, multilymphoid progenitor; NeP, neutrophil progenitor; NK, natural killer cell; Pre-B, precursor B cell; Pro-B, progenitor B cell; Rel, relapse.

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