Spatial Immune Remodeling Across the Gallbladder Carcinogenesis Spectrum: A Multicenter Digital Pathology Study

Area of Science:

• Oncology
• Immunology
• Digital Pathology

Background:

• Gallbladder carcinoma (GBC) is aggressive, often diagnosed late with metastasis.
• The tumor immune landscape during GBC development is poorly understood.
• Understanding immune changes is crucial for GBC diagnosis and treatment.

Purpose of the Study:

• To quantitatively assess immune microenvironment alterations in gallbladder lesions.
• To analyze immune cell distribution across the spectrum of gallbladder carcinogenesis.
• To identify potential immune biomarkers for GBC aggressiveness.

Main Methods:

• Retrospective multicenter study of 90 gallbladder specimens.
• Immunohistochemistry for CD8, FOXP3, and CD163.
• Digital pathology analysis for immune cell quantification and spatial distribution.
• Calculation of composite immune indices, including an immune suppression index.

Main Results:

• Progressive immune landscape remodeling observed across gallbladder lesions.
• Increased infiltration of regulatory T cells (FOXP3) and macrophages (CD163) in dysplasia and tumors.
• Cytotoxic T lymphocytes (CD8) showed spatial exclusion from tumor centers.
• Metastatic tumors had lower CD8+ T cells and higher immunosuppressive cells, with elevated immune suppression indices.

Conclusions:

• Gallbladder carcinogenesis involves immune microenvironment remodeling with immunosuppressive cell enrichment.
• Spatial restriction of cytotoxic T lymphocytes is observed in GBC.
• Digital pathology offers a reproducible method for assessing tumor-immune interactions.
• Immune architecture analysis may yield biomarkers for GBC aggressiveness.