Extended Data Fig. 4: Cellular neighborhood analysis of residual HCC. | Nature Cancer

Extended Data Fig. 4: Cellular neighborhood analysis of residual HCC.

From: Spatial analysis reveals targetable macrophage-mediated mechanisms of immune evasion in hepatocellular carcinoma minimal residual disease

Extended Data Fig. 4: Cellular neighborhood analysis of residual HCC.

a. Cross-matching of Voronoi plots showing spatial neighborhoods and the associated H&E and CODEX immunofluorescence staining images representations of the same tumor core. The canonical markers of key cells represented in each neighborhood are shown. b. Stacked bar chart comparing relative proportions of all 9 cellular neighborhoods identified by CODEX by HCC AJCC Stage (I n=58 vs II-III n=50 patients), grade (1 n=40, 2 n=57, and 3 n=9 patients), and etiologies (NASH n=28 patients, ALD n=11 patients, HepC n=35 patients, and HepB n=21 patients). c. Boxplot comparisons of CK19, EpCAM, CD3, aSMA, CD15, and CD68 expression amongst the identified cellular neighborhoods (CK19+Tumor CN=33708 cells, EpCAM+ Tumor CN=28190, Fibroinflammatory immune CN= 140,273, Innate immune CN= 53,912, M2-macrophage Immune CN= 188,407, Other= 6,130, T cell Immune CN=51,987, Pauci-immune tumor CN=310,977, Vascular inflammatory Tumor CN=251,581). Box: 25–75 percentile, whiskers: 5–95 percentile, line: median. d. Comparison of proportion of EpCAM+ tumor cells and exhausted CD8 T cells in residual HCC stratified by median frequency of M2-macrophage CN (Low n=17; High n=38 patients). e. Comparison of specific canonical marker expression on macrophage and T cells in the EpCAM+ tumor CN (macrophages n=272 cells, T cells n=13 cells), CK19+ tumor CN (macrophages n=1201 cells, T cells n=354 cells) compared to vascular inflammatory tumor CN (macrophages n=16143 cells, T cells n=1275 cells) in residual HCC. Abbreviations: H&E-hematoxylin and eosin, HCC- hepatocellular carcinoma, CODEX- co-detection by indexing, NASH-nonalcoholic steatohepatitis, ALD- alcoholic liver disease, HepC- hepatitis C, HepB- hepatitis B, CK- cytokeratin, CD- cluster of differentiation, EPCAM- epithelial cell adhesion molecule, aSMA- alpha smooth muscle actin, CN- Cellular neighborhood, PD1- programmed cell death protein 1, TIM3- T cell immunoglobulin and mucin domain-containing protein 3, Macro- macrophages, DAPI-4′,6-diamidino-2-phenylindole, PanCK- Pan-cytokeratin, ECad- E cadherin.

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