Imaging mass cytometry of the immune microenvironment in alveolar echinococcosis.

BACKGROUND

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis, is a severe parasitic disease exhibiting tumor-like growth and profound immune evasion. The spatial organization and immunosuppressive mechanisms within the human AE lesion microenvironment remain poorly characterized.

METHODS

High-dimensional imaging mass cytometry (IMC) was performed on liver tissue sections from six patients with histologically confirmed AE, comparing lesion-proximal (close liver tissue, CLT) and lesion-distal (distant liver tissue, DLT) regions. This approach enabled simultaneous profiling of immune cell infiltration, spatial heterogeneity, immune checkpoint expression, and microenvironmental architecture. Complementary immunofluorescence and immunohistochemistry were used to evaluate age-related differences in neutrophil subsets between pediatric and adult patients.

RESULTS

Sixteen immune cell types were resolved by IMC, revealing distinct spatial distributions: CD15- neutrophils and CD4+ effector memory T (Tem) cells accumulated in partially necrotic zones; M1/M2 macrophages and dendritic cells formed ring-like structures around cytotoxic T lymphocyte (CTL)-rich areas; CD4+ and CD8+ effector T cells exhibited dispersed circular patterns. M2 macrophages showed a negative correlation with T cells-suggesting T cell exhaustion-and a positive association with CD15+ neutrophils but not CD15-neutrophils. Immune checkpoint molecules were generally expressed at low levels in CLT, with focal PD-1/PD-L1 co-expression, broad CD47 distribution, rare NKG2A+ cells, and TIGIT enrichment in innate NK cells. Based on the TIMELASER classification system, the AE immune microenvironment was categorized into three subtypes: marrow-enriched immunosuppressive, stroma-enriched immunosuppressive, and immune-resident. Significantly higher densities of both CD15+ and CD15- neutrophils were observed in CLT of pediatric patients compared to adults.

CONCLUSION

This study provides the first spatially resolved map of the immune landscape in human AE, revealing dynamic immunosuppressive niches shaped by myeloid-lymphoid crosstalk and checkpoint regulation. These findings offer new insights into early immune evasion mechanisms and potential targets for host-directed therapeutic strategies.