Related Experiment Video

Updated: Dec 27, 2025

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
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Programmed Cell Death Ligand Expression Drives Immune Tolerogenesis across the Diverse Subtypes of Neuroendocrine

David J Pinato1, Anu Vallipuram2, Joanne S Evans2

  • 1Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom, david.pinato@imperial.ac.uk.

Neuroendocrinology
|February 26, 2020
PubMed
Abstract

Insights

Programmed cell death-1 ligand (PD-L1) expression in neuroendocrine tumors (NETs) correlates with T-cell exhaustion and is found in circulating tumor cells. This suggests PD-L1 inhibitors may benefit a subset of NET patients.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Comprehensive characterization of the tumor microenvironment in neuroendocrine tumors (NETs) is lacking.
  • Programmed cell death-1 receptor-ligand (PD-1/PD-L1) inhibitors are being tested for NET efficacy.

Purpose of the Study:

  • Investigate drivers of cancer-related immunosuppression in NETs.
  • Analyze PD-1/PD-L1 expression in relation to tumor characteristics and immune cells.

Main Methods:

  • Multi-parameter immunohistochemistry on tissue microarrays (n=102) for PD-L1, PD-L2, and IDO-1.
  • Evaluation of tumor-infiltrating lymphocytes (TILs), hypoxia, and angiogenesis biomarkers.
  • Targeted transcriptomic profiling and PD-L1 testing in circulating tumor cells (CTCs, n=12).

Main Results:

  • PD-L1 expression was highest in lung NETs; PD-L2 was highest in pancreatic NETs.
  • PD-L1+ NETs showed increased CD4+/FOXP3+ and CD8+/PD1+ TILs and necrosis.
  • PD-L1 expression correlated with T-cell exhaustion, independent of tumor hypoxia.
  • PD-L1+ CTC subpopulations were identified in 75% of patients.

Conclusions:

  • PD-L1 expression is relevant to NET progression and T-cell exhaustion.
  • PD-L1 inhibitors may offer therapeutic potential for a subset of NET patients.
Keywords:
Neuroendocrine tumoursPD-1PD-L1PD-L2

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