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Population-Specific Immunogenomic Alterations in Gallbladder Cancer and Prognostic Significance.

Yan Zhu1, Luisa Maren Solis Soto2, Shubham Pant3

  • 1Department of Translational Molecular Pathology, MD Anderson Cancer Center, The University of Texas, Houston, Texas; Cancer Biology Program, MD Anderson Cancer Center, The University of Texas, UTHealth Graduate School of Biomedical Sciences, Houston, Texas.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|June 20, 2025
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Summary

Gallbladder cancer immunogenomics differ by geography. Latin American patients show distinct immune profiles, suggesting location impacts therapeutic strategies for this deadly cancer.

Keywords:
ChileUnited States of Americagallbladder cancerimmune markersmutation

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Gallbladder carcinoma has a poor prognosis, with limited benefit from current immunotherapies like PD1/PDL1 inhibitors.
  • Understanding the global immunogenomic landscape is crucial for optimizing cancer treatment.

Purpose of the Study:

  • To create detailed immunogenomic landscapes of gallbladder cancer from US and Chilean patient cohorts.
  • To identify distinct immune profiles and potential biomarkers for improved therapeutic strategies.

Main Methods:

  • Targeted next-generation sequencing and immunohistochemistry were used on 122 gallbladder cancer cases (60 US, 62 Chile).
  • Multiplexed single-cell imaging technology was employed to analyze immune cell populations.

Main Results:

  • Shared mutations (e.g., TP53, KRAS) and amplifications (e.g., ERBB2, CCNE1) were identified in both cohorts.
  • Distinct immune profiles were observed: higher CD4+ T cell and PD-1 densities, but lower CD68+ macrophage densities in the Latin American cohort.
  • Low CD4 and high V-domain Ig suppressor of T cell activation identified as a potential biomarker pair for poor outcomes.

Conclusions:

  • Geographic location significantly influences the immunogenomic landscape of gallbladder carcinoma.
  • Novel immune subgroups and clinical associations were identified, independent of specific mutations.
  • Findings emphasize the need for geographically sensitive therapeutic development in gallbladder cancer.