ArticleCancers2020
Immunoprofiling in Neuroendocrine Neoplasms Unveil Immunosuppressive Microenvironment.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Immunogenic cell death as a mechanism of synergy between sunitinib andCell death discovery · 2026Article
- Unravelling mesenteric fibrosis in small intestinal neuroendocrine tumours and implications for clinical management.Endocrine-related cancer · 2026Review
- The metastatic spectrum in functional and non-functional NENs: mechanistic insights from multi-omics.Frontiers in endocrinology · 2026Review
- The Role of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Tumors.International journal of molecular sciences · 2025Review
- Review
- Article
- Spatial profiling reveals tissue-specific neuro-immune interactions in gastroenteropancreatic neuroendocrine tumors.The Journal of pathology · 2024Article
- Defining Tumor Microenvironment as a Possible Target for Effective GEP-NENs Immunotherapy-A Systematic Review.Cancers · 2023Review
- Combined tubular adenocarcinoma, neuroendocrine carcinoma and adenocarcinoma with enteroblastic differentiation arising in Barrett esophagus.Clinical journal of gastroenterology · 2023Article
- Artificial Intelligence-Powered Whole-Slide Image Analyzer Reveals a Distinctive Distribution of Tumor-Infiltrating Lymphocytes in Neuroendocrine Neoplasms.Diagnostics (Basel, Switzerland) · 2022Article
- Review
- The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms.Cancers · 2022Review
- Evolving role of seneca valley virus and its biomarker TEM8/ANTXR1 in cancer therapeutics.Frontiers in molecular biosciences · 2022Review
- Elevated Flt3L Predicts Long-Term Survival in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms.Cancers · 2021Article
- Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Checkpoint inhibitors have shown promising results in a variety of tumors; however, in neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC), low response rates were reported. We aimed herein to investigate the tumor immune microenvironment in NET/NEC to determine whether checkpoint pathways like programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) might play a role in immune escape and whether other escape mechanisms might need to be targeted to enable a functional antitumor response. Forty-eight NET and thirty NEC samples were analyzed by immunohistochemistry (IHC) and mRNA immunoprofiling including digital spatial profiling. Through IHC, both NET/NEC showed stromal, but less intratumoral CD3+ T cell infiltration, although this was significantly higher in NEC compared to NET. Expression of PD1, PD-L1, and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on immune cells was low or nearly absent. mRNA immunoprofiling revealed low expression of IFNγ inducible genes in NET and NEC without any spatial heterogeneity. However, we observed an increased mRNA expression of chemokines, which attract myeloid cells in NET and NEC, and a high abundance of genes related to immunosuppressive myeloid cells and genes with immunosuppressive functions like CD47 and CD74. In conclusion, NET and NEC lack signs of an activation of the adaptive immune system, but rather show abundance of several immunosuppressive genes that represent potential targets for immunomodulation.
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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.