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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Related Experiment Video

Updated: Jul 16, 2026

Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
11:00

Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment

Published on: March 25, 2020

Single-Cell and Spatial Transcriptomics Reframe the Immunosuppressive Microenvironment of Neuroendocrine Neoplasms.

Yoshihiro Takahashi1,2, Shin Tsunekawa1,3

  • 1Department of Diabetes, Endocrinology and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.

Cancers
|July 15, 2026
PubMed
Summary

Neuroendocrine neoplasms (NENs) are not entirely immune cold. Advanced single-cell and spatial transcriptomics reveal multilayered immunosuppression mechanisms beyond PD-1/PD-L1, guiding new neuroendocrine tumor therapies.

Keywords:
immunosuppressionneuroendocrine neoplasmsprecision immuno-oncologysingle-cell RNA sequencingspatial transcriptomicstumor microenvironment

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Multiplex Immunohistochemical Analysis of the Spatial Immune Cell Landscape of the Tumor Microenvironment
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Multiplex Immunohistochemical Analysis of the Spatial Immune Cell Landscape of the Tumor Microenvironment

Published on: August 18, 2023

Related Experiment Videos

Last Updated: Jul 16, 2026

Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
11:00

Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment

Published on: March 25, 2020

Multiplex Immunohistochemical Analysis of the Spatial Immune Cell Landscape of the Tumor Microenvironment
06:32

Multiplex Immunohistochemical Analysis of the Spatial Immune Cell Landscape of the Tumor Microenvironment

Published on: August 18, 2023

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Neuroendocrine neoplasms (NENs) are often considered "immune cold" and resistant to PD-1/PD-L1 blockade.
  • Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics offer new insights into the NEN tumor microenvironment (TME).

Purpose of the Study:

  • To integrate scRNA-seq and spatial transcriptomic data across NEN subtypes.
  • To reframe the understanding of NEN immunosuppression.
  • To identify translational implications for NEN treatment.

Main Methods:

  • Structured narrative review of PubMed-indexed studies up to April 2026.
  • Prioritization of human scRNA-seq, single-nucleus RNA-seq, spatial transcriptomic, and spatial proteomic studies.
  • Inclusion of mechanistic, clinical, and biomarker-focused reports.

Main Results:

  • Conserved immunosuppressive features across NEN subtypes (pancreatic, pulmonary, GI, etc.) beyond PD-1/PD-L1.
  • Myeloid infiltration with alternative checkpoints (VISTA, TIM-3, Galectin-9).
  • Cancer-associated fibroblast-mediated immune exclusion and neuroendocrine secretory product immunomodulation.

Conclusions:

  • NEN immunosuppression is a complex, multilayered, and subtype-dependent process.
  • A four-layer framework integrates mechanisms, biomarkers, and therapies.
  • These findings support biomarker-guided, subtype-adapted therapeutic strategies in neuroendocrine oncology.