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Updated: Apr 7, 2026
Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection
Published on: July 6, 2022
Spatial immune profiling complements genomic sequencing in biliary tract cancer: hypothesis-generating use cases
M Barsch1, I Godbole1, P Metzger2
1Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Background:
Personalized therapy approaches targeting homologous recombination deficiency (HRD) in biliary tract cancer (BTC) remain poorly explored with limited clinical data available. Beyond BRCA1/2, the therapeutic implications of BRCA1-associated protein 1 (BAP1) alterations are unclear.
Materials And Methods:
We describe three patients with BTC and HRD-related mutations as hypothesis-generating use cases. We illustrate how integration of multiplexed imaging mass cytometry-based spatial immune profiling with genomic sequencing may help generate testable biological hypotheses beyond genomics alone.
Results:
A patient with germline BRCA2-mutated BTC together with a positive HRD score was sensitive to platinum-based therapy and poly (ADP-ribose) polymerase inhibition. In contrast, a patient with loss of BAP1 was linked to a CD8+ T-cell enriched tumor microenvironment, classified as spatially immune enriched and responded long-term to subsequent immune checkpoint inhibition and tyrosine kinase inhibition therapy.
Conclusion:
These observations provide a rationale for integrated genomic and spatial immune profiling in BTC, which will require further prospective validation.
