Samsung Medical Center Presents World's First "Immune Map" of Ampulla of Vater Carcinoma

Identifying Four Molecular Subtypes Through Single-Cell and Spatial Transcriptomics Analyses

The research team at Samsung Medical Center has subdivided the rare cancer ampulla of Vater carcinoma into four molecular subtypes and found that a specific subtype has the poorest prognosis. Through single-cell transcriptomics and spatial transcriptomics analyses, they also identified unique characteristics of the tumor microenvironment.

Research team identifying four molecular subtypes of Barrett's esophagus. From left, Professor Jookyung Park, Department of Gastroenterology, Samsung Medical Center; Professor Gitaek Jang, Department of Pathology; Professor Semin Lee, Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST). Samsung Medical Center.

On August 12, Samsung Medical Center announced that the teams led by Professor Jukyung Park from the Department of Gastroenterology and Professor Gitaek Jang from the Department of Pathology, together with Professor Semin Lee from the Department of Biomedical Engineering at Ulsan National Institute of Science and Technology (UNIST), analyzed the molecular characteristics of cancer cells using single-cell transcriptomics on samples from 70 patients with ampulla of Vater carcinoma.

As a result, ampulla of Vater carcinoma was classified into four subtypes: Int-Wnt, Int-Hypoxia, PB-KRAS, and Cycling. Previously, this carcinoma was broadly divided histologically into either the intestinal type or the pancreaticobiliary type.

Within the intestinal type, two subtypes were identified: the Int-Wnt type, characterized by the activation of signals that promote cancer cell growth, and the Int-Hypoxia type, defined by pathways responsive to hypoxic conditions. In the pancreaticobiliary type, the PB-KRAS type was identified, marked by strong KRAS signaling that increases the malignancy of the cancer, and the Cycling type, which features high levels of cell division.

Notably, patients with a high proportion of the PB-KRAS type were found to have a 116.6-fold higher risk of death compared to those without a high PB-KRAS ratio. This subtype exhibited greater genomic instability than the others, along with increased KRAS gene expression and enhanced self-proliferating and regenerative abilities in cancer cells.

The team also conducted spatial transcriptomics analyses following single-cell transcriptomics, enabling them to examine the tumor microenvironment surrounding cancer cells. By analyzing the location and interactions between cancer and immune cells, they mapped out the immune landscape within the tumor.

Schematic diagram illustrating the characteristics of the Barrett's esophagus subtype identified by the research team. Samsung Medical Center

The results showed that the area surrounding the PB-KRAS type subtype was densely populated by cytotoxic T cells (GZMK+ CD8 T cells) with impaired immune function and macrophages (SPP1+ macrophages) that suppress immune responses.

Additionally, immunosuppressive signals such as TGFB2, SPP1, and FGF2 were detected. These findings suggest that the PB-KRAS type may create an immunosuppressive microenvironment around itself, aiding the cancer cells in evading immune attacks. The research team believes that these characteristics might explain the poor responsiveness of this subtype to immunotherapy drugs.

Ampulla of Vater carcinoma develops in the ampulla of Vater, where the bile duct and pancreatic duct meet the duodenum. According to the 2026 statistics released by the Korea Central Cancer Registry, there are 864 new cases of ampulla of Vater carcinoma per year in Korea, accounting for about 0.3% of all cancers. Due to its low incidence, related research and clinical trials are limited, making the development of new treatments challenging.

Professor Park, who led the research, stated, "With this study, we have identified the molecular mechanisms underlying the aggressiveness of ampulla of Vater carcinoma at the cellular level. We hope that these findings will help in the early identification of high-risk groups for relapse and the development of new therapeutic strategies targeting KRAS and immunosuppressive signals." The study was published in a recent issue of the international journal Biomarker Research.

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