The application of imaging mass cytometry in the immune microenvironment of alveolar echinococcosis.

BACKGROUND

Hepatic alveolar echinococcosis (HAE) is a chronic parasitic disease caused by infection with the larval form of Echinococcus multilocularis, characterised by the formation of invasive lesions in the liver, which involve the proliferation of immune system cells in response to the pathogen. Although surgical resection is the treatment of choice, patients in advanced stages often lose the opportunity for surgery, and drug therapy has limited efficacy. The immune microenvironment plays a key role in tumour progression, but its spatial heterogeneity in HAE has not yet been systematically elucidated.

METHODS

Tissue samples for this study were obtained from the tissue proximal to the lesion and matched distal liver tissue from three patients with HAE. Imaging mass cytometry (IMC) analysis was performed using an antibody panel comprising 28 immunological markers. PhenoGraph clustering and t-SNE dimensionality reduction techniques were applied to classify and visualise single-cell data, and to analyse spatial interactions between cells.

RESULTS

Both the tissue proximal to the lesion and the distal liver tissue exhibited significant immune cell infiltration and marked spatial heterogeneity. The tissue proximal to the lesion was characterised primarily by activated CD8+ T cells (Cluster 3/19) and CD56+ NK cells (Cluster 17/18), presenting an immune-activated state and forming tertiary lymphoid structure (TLS)-like structures. B cells (Cluster 1) were reduced in number in the proximal lesion, whilst macrophages (Cluster 6) showed significant colocalisation with B cells, suggesting that macrophages may regulate B cell function through processes such as antigen presentation.

CONCLUSION

This study utilised IMC technology to reveal the complex landscape and heterogeneity of the HAE immune microenvironment, providing new targets and insights for the development of immunotherapeutic strategies for this disease.