Abstract
Single-cell imaging mass cytometry identifies phenotypic subsets of metastatic gastroenteropancreatic neuroendocrine tumors
European journal of surgical oncology, Vol.50(Supplement 2), pp.129-130
12/2024
DOI: 10.1016/j.ejso.2024.109201
Abstract
Background: Epigenetic alterations in immune cells, stroma, and extracellular matrix (ECM) of Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) microenvironment (TME) may account for changes in metastasis and tumor progression. However, current management guidelines of metastatic GEP-NET do not take these molecular changes into consideration for this clinico-pathological heterogenous group. We used single-cell imaging mass cytometry (IMC) to identify specific phenotypic subsets of GEP-NET and their spatial relationships within the TME.
Material and methods: A total of 24 patients with metastatic ileal (n = 13) and pancreatic (n = 11) GEP-NETs were included. Tissue microarrays were created using tumor (T), lymph node (LN), liver metastasis (L) and normal tissue (N). Overall (OS) and progression-free survival (PFS) were also recorded. IMC was used to simultaneously quantify protein expression using a metal-tagged antibody panel (n = 42) to identify tumor, stromal, and immune phenotypes within small bowel (SB) and pancreatic GEP-NET at the primary tumor, lymph nodes and sites of metastases. Phenotypic densities at tumor rich sites were correlated with PFS and OS.
Results (For Surgical Trial Proposals fill in ‘the Feasibility’, for Surgical Trial in Progress fill in the ‘Current status’): Spatial proteogenomic TME analysis revealed 12 distinct cellular clusters and 12 cellular neighborhoods. Increased phenotypic density of cancer-associated fibroblasts (CAF) in PNET liver metastasis was associated with PFS (p=0.01), versus CD4 cell and M1 macrophage infiltration for SB-NET (p < 0.05). Additionally, plasmacytoid dendritic cells (pDC) at the site of PNET lymph node metastasis were associated with OS (p = 0.02).
Conclusions (For Surgical Trial in Progress and Surgical Trial Proposals fill in ‘NA’): Single-cell IMC characterizes the GEP-NET TME profile specifically with respect to immune and stromal subsets and their spatial relationships. M1 macrophage and CD4 cell infiltration in SB-NET and CAF density within liver metastasis for PNET were associated with PFS. To our knowledge, this is the first report to utilize single-cell IMC to characterize the GEP-NET TME at single-cell spatial resolution across primary tumor and multiple metastatic sites. This may allow to personalize prognostication and help guide future immune-directed therapy.
Details
- Title: Subtitle
- Single-cell imaging mass cytometry identifies phenotypic subsets of metastatic gastroenteropancreatic neuroendocrine tumors
- Creators
- T. Dumitra - Cedars-Sinai Medical CenterE. Pletcher - Cedars-Sinai Medical CenterS. Mahov - Cedars-Sinai Medical CenterA. Bellizzi - University of IowaM. Justo - Cedars-Sinai Medical CenterA. Xu - Cedars-Sinai Medical CenterA. Merchant - Cedars-Sinai Medical CenterJ.R. Howe - University of IowaA. Gangi - Cedars-Sinai Medical Center
- Resource Type
- Abstract
- Publication Details
- European journal of surgical oncology, Vol.50(Supplement 2), pp.129-130
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.ejso.2024.109201
- ISSN
- 0748-7983
- Language
- English
- Date published
- 12/2024
- Academic Unit
- Pathology; Surgery
- Record Identifier
- 9984759889102771
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