Spatial immune profiling complements genomic sequencing in biliary tract cancer: hypothesis-generating use cases
Year: 2026
Type: article
Study design: Case Report
Abstract: 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.
Source: ESMO Gastrointestinal Oncology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,170
Awards: G1598854997, Verbund SATURN3 - Räumliche und zeitliche Auflösung der intratumoralen Heterogenität bei den drei schwer zu behandelnden Krebsarten Brustkrebs, Darmkrebs und Bauchspeicheldrüsenkrebs, Standort Universität Köln, G2050369189, Regulation der T Zellerschöpfung bei der chronischen Hepatitis B – Infektion und dem Hepatozellulärem Karzinom, G3229666995, PM4Onco - Medizininformatik-Use Case 'Personalisierte Medizin für die Onkologie' - Teilvorhaben: Koordination, Integration Krebsregisterdaten, Patient Journey, Kerndatensätze, Bioinformatik-/Dateninfrastrukturen, Erweiterte Analytik und Roll-Out: UK Freiburg, SFB 1479: Onkogengetriebener Immun Escape (OncoEscape), SFB 1453: Nephrogenetik (NephGen), SFB 1160: Immunpathologie aufgrund eingeschränkter Immunreaktionen (IMPATH), TRR 167: Entwicklung, Funktion und Potential von myeloiden Zellen im zentralen Nervensystem (NeuroMac), G849492958, TRR 353: Regulation von Entscheidungen in Zelltodprozessen, G8877722204
OpenAlex ID: W7140138568