Skip to main content
. 2022 Jul 13;11(6):540–557. doi: 10.1159/000525375

Fig. 5.

Fig. 5

SULF2 expression characterizes an immune HCC phenotype, with stromal SULF2 upregulating CCL2 inducing, an altered macrophage phenotype and accumulation of macrophage in tumours. a SULF2 expression in HCC patients with an immune-exhausted phenotype was higher than patients with resting and immune active phenotypes (p< 0.001, independent sample Kruskal-Wallis test, n = 370 patients). b Heatmap of TCGA patients classified as Immune (exhausted and active) or nonimmune (rest) illustrates further how SULF2 expression correlates with TGFβ1 signalling, TGFβ1 regulated signatures (TBRS), and immune signatures. The median of the enrichment score in each class is shown on the right, with the percentage of patients in each class with enrichment of the WNT-TGFB signature. An ELISA assay confirmed SULF2 overexpression in LX-2 CM, with promoted secretion of CCL2 shown in (ci). ciiCCL2 mRNA was suppressed in SULF2 KD COS-7 cells. diLX-2 SULF2-CM preferentially increased transwell migration of monocytes (macrophage precursors) relative to LX-2-CM. diiCharacterization of CM activated CD80 expressing monocytes revealed an altered phenotype, with reduced expression of CX3CR1, HLADR, and CD86 in the presence of SULF2. Representative images of H&E, SULF2, CD68, and CD163 immunohistochemistry in patients with low (e) versus high (f) tumour stromal SULF2 expression showed higher numbers of CD68 or CD163 positive macrophages in tumours with high SULF2.