ArticleGut2021
Immune landscape, evolution, hypoxia-mediated viral mimicry pathways and therapeutic potential in molecular subtypes of pancreatic neuroendocrine tumours.
Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
44 citing papers in PubMed, 51 citations in OpenAlex.
- Single-Cell and Spatial Transcriptomics Reframe the Immunosuppressive Microenvironment of Neuroendocrine Neoplasms.Cancers · 2026Review
- Multi-omics profiling of pancreatic neuroendocrine tumors: Interplay of genomic instability and the tumor microenvironment (Review).Oncology letters · 2026Review
- Distinct Malignant Cell States and Myeloid Glutamate Signaling Associated with Aggressive Pancreatic Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape.Molecular cancer · 2026Review
- Integrated genomics and transcriptomics reveal key events in pancreatic neuroendocrine neoplasm.BMC biology · 2026Article
- Calcium Channel Blockers Inhibit Pancreatic Neuroendocrine Neoplasms Progression via Cav1.2-Epigenetic Circuit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rethinking gastroenteropancreatic neuroendocrine neoplasms: A perspective on cellular origins, molecular mechanisms, and combination therapies.Journal of translational internal medicine · 2026Article
- Immunosuppressive Environment of Pancreatic NENs-A Review.Biomedicines · 2026Review
- Concept of neuroendocrine neoplasms of all organs with a focus on grading, subtyping.Virchows Archiv : an international journal of pathology · 2026Review
- Arteriolar angiogenesis: implications in anti-angiogenic immunotherapy for pancreatic cancers.Cytokine & growth factor reviews · 2025Review
- Updates on radiotherapy-immunotherapy combinations: Proceedings of 8th Annual ImmunoRad Conference.Oncoimmunology · 2025Article
- Translational biomarkers of hypoxic brain injury uncovered in CSF secreting human choroid plexus organoids.Fluids and barriers of the CNS · 2025Article
- Molecular Subtypes of Pancreatic Neuroendocrine Tumors Mutated in MEN1/DAXX/ATRX Explain Biological Variability.Endocrine pathology · 2025Article
- Prognostic Features in Surgically Resected Well-Differentiated Pancreatic Neuroendocrine Tumors: an Analysis of 904 Patients with 7882 Person-Years of Follow-Up.Endocrine pathology · 2025Article
- The Role of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Tumors.International journal of molecular sciences · 2025Review
- Basic science and translational implications of current knowledge on neuroendocrine tumors.The Journal of clinical investigation · 2025Review
- [Asia Oceania journal of nuclear medicine & biology · 2025Article
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- Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion.Cancer immunology research · 2024Article
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 4 countries.
Funding
Abstract
objectiveA comprehensive analysis of the immune landscape of pancreatic neuroendocrine tumours (PanNETs) was performed according to clinicopathological parameters and previously defined molecular subtypes to identify potential therapeutic vulnerabilities in this disease.
designDifferential expression analysis of 600 immune-related genes was performed on 207 PanNET samples, comprising a training cohort (n=72) and two validation cohorts (n=135) from multiple transcriptome profiling platforms. Different immune-related and subtype-related phenotypes, cell types and pathways were investigated using different in silico methods and were further validated using spatial multiplex immunofluorescence.
resultsThe study identified an immune signature of 132 genes segregating PanNETs (n=207) according to four previously defined molecular subtypes: metastasis-like primary (MLP)-1 and MLP-2, insulinoma-like and intermediate. The MLP-1 subtype (26%-31% samples across three cohorts) was strongly associated with elevated levels of immune-related genes, poor prognosis and a cascade of tumour evolutionary events: larger hypoxic and necroptotic tumours leading to increased damage-associated molecular patterns (viral mimicry), stimulator of interferon gene pathway, T cell-inflamed genes, immune checkpoint targets, and T cell-mediated and M1 macrophage-mediated immune escape mechanisms. Multiplex spatial profiling validated significantly increased macrophages in the MLP-1 subtype.
conclusionThis study provides novel data on the immune microenvironment of PanNETs and identifies MLP-1 subtype as an immune-high phenotype featuring a broad and robust activation of immune-related genes. This study, with further refinement, paves the way for future precision immunotherapy studies in PanNETs to potentially select a subset of MLP-1 patients who may be more likely to respond.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.