ArticleFrontiers in oncology2019
PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity.
Article in Frontiers in oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 72 citations in OpenAlex.
- Gastric Carcinoma with Exocrine and Neuroendocrine Components: A 16-Year Cohort Analysis and International Comparison.Current oncology (Toronto, Ont.) · 2026Article
- The Role of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Tumors.International journal of molecular sciences · 2025Review
- The role of immune cells phenotype in neuroendocrine tumors development.Discover oncology · 2025Article
- A phase 1 study to assess the safety, tolerability and effectiveness of PV-10 (Rose Bengal Sodium) in neuroendocrine tumours metastatic to the liver.British journal of cancer · 2025Article
- The Spatial Proximity of CD8Current oncology (Toronto, Ont.) · 2025Article
- Basic science and translational implications of current knowledge on neuroendocrine tumors.The Journal of clinical investigation · 2025Review
- Neuroendocrine Neoplasms of the Breast: Current Insights and Future Directions.Cancer reports (Hoboken, N.J.) · 2024Review
- Immunotherapy for gastric cancer and liver metastasis: Is it time to bid farewell.World journal of gastrointestinal surgery · 2024Article
- Neuroendocrine neoplasms of the breast: a review of literature.Virchows Archiv : an international journal of pathology · 2024Review
- Review
- Spatial profiling reveals tissue-specific neuro-immune interactions in gastroenteropancreatic neuroendocrine tumors.The Journal of pathology · 2024Article
- Correlation of Neuroendocrine Differentiation with a Distinctively Suppressive Immune Microenvironment in Gastric Cancer.Neuroendocrinology · 2024Article
- Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.Cancer metastasis reviews · 2023Review
- HIF: a master regulator of nutrient availability and metabolic cross-talk in the tumor microenvironment.The EMBO journal · 2023Review
- High-Frequency Nanosecond Bleomycin Electrochemotherapy and its Effects on Changes in the Immune System and Survival.Cancers · 2022Article
- Evaluation of PD-L1 expression in a large set of gastroenteropancreatic neuroendocrine tumours and correlation with clinicopathological data.Translational oncology · 2022Article
- The expression profiles of CD47 in the tumor microenvironment of salivary gland cancers: a next step in histology-driven immunotherapy.BMC cancer · 2022Article
- Artificial Intelligence-Powered Whole-Slide Image Analyzer Reveals a Distinctive Distribution of Tumor-Infiltrating Lymphocytes in Neuroendocrine Neoplasms.Diagnostics (Basel, Switzerland) · 2022Article
- Sintilimab in Patients with Previously Treated Metastatic Neuroendocrine Neoplasms.The oncologist · 2022Article
- The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms.Cancers · 2022Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC).
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