Fig. 4: Identification of six distinct tumor microenvironment (TME) archetypes.

a Heatmap showing scaled cell-type abundance from the invasive margin regions of interest (ROIs). Six TME archetypes are clustered by the level of selected cell types (MC2, Tumor CAIX⁺, B, CD4⁺ T, CD8⁺ T, and MC4 cells). b TME archetype patterns of each patient. If all ROIs from one patient are classified as having the same TME archetype, the patient is marked as the corresponding color of TME archetype. Patients who have ROIs that contain heterogeneous TME archetypes are indicated with magenta. c An example ROI from each TME archetype with hematoxylin and eosin (HE)-stained image (top) and its corresponding imaging mass cytometry image (bottom) with cell phenotyping (B, CD4⁺ T, CD8⁺ T, MC2, and MC4 cells). d Gene set enrichment analysis (GSEA) of genes upregulated expressed in patients with each TME archetype (the number of patients with C1, C2, C3, H1, H2, and H3 TME archetype are 6, 2, 5, 3, 6, and 2, respectively). Significantly enriched gene sets (adjusted P < 0.05, Benjamini–Hochberg method) from MSigDB HALLMARK collection are shown. There is no significant pathway enriched in samples with C2 TME archetype based on the 0.05 threshold for adjusted P value. e Kaplan–Meier curves of overall survival (left) and progression-free survival (right) for melanoma patients based on their TME archetypes (n = 13 patients with immune cold TME, n = 11 patients with immune hot TME). P values calculated using log-rank test. f Histograms showing the nearest distance in μm between CD8⁺ T cells and other immune cells. MC1: HLA-DR⁻CD14⁺CD11c⁺ myeloid cells, MC2: HLA-DR⁻CD14⁺ myeloid cells, MC3: HLA-DR⁻CD11b^hi myeloid cells, MC4: HLA-DR^hiCD14^hiCD16⁺CD11c⁺CD11b⁺ myeloid cells, MC5: HLA-DR⁺CD14^hiCD16⁺CD11b⁺ myeloid cells, MC6: HLA-DR⁺CD14⁺ myeloid cells.