Comparative analysis of T-cell exhaustion in hematologic and solid malignancies. (A) T-cell exhaustion and memory scores calculated for CD8⁺ T cells from healthy bone marrow, AML and chronic myeloid leukemia bone marrow and different solid tumors including basal cell carcinoma, bladder cancer and metastatic melanoma. (B) Expression of CTLA-4, PDCD1 (encoding PD-1) and ENTPD1 (encoding CD39) across T-cell subsets in AML bone marrow (top, n = 18 patients) and in metastatic melanoma (bottom, n = 4 patients; Oliveira et al³⁶). (C) Bulk RNA sequencing (RNA-seq) expression of ZNF683 and KLRB1 across 29 AML/MDS bone marrow biopsies with disease involvement and 21 extramedullary AML (eAML) biopsies from patients with sole extramedullary relapse. (D) Ratio of CTLA-4 and KLRB1 to CD3 expression obtained from bulk RNA-seq data across AML/MDS and eAML. Statistical testing using 2-sided t-test. (E) Percentage of CD3⁺ T-cell infiltrate (left), CD103⁺ T cells (middle) and FOXP3⁺ CTLA-4⁺ T cells (right) compared between bone marrow (BM; n = 10) and leukemia cutis (eAML; n = 10) before treatment. The exceptional responder with ongoing complete remission >3 years after treatment with decitabine and ipilimumab is indicated by the blue arrow. Statistical testing with 2-sided t-test. Medians are indicated for each group by the horizontal bar. (F) Representative single stains of CD3 (white), CD103 (red), CTLA-4 (cyan) and FOXP3 (yellow) for bone marrow (BM) and leukemia cutis (eAML) (top). Integrated staining of CD3, FOXP3 and CTLA-4 is shown for BM and eAML (bottom). The images were captured with 20× optical magnification and 250% zoom. Yellow bars indicate a distance of 50 μm.