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Review
. 2025 Apr;14(7):e70798.
doi: 10.1002/cam4.70798.

Characterization of the Pancreatic Neuroendocrine Neoplasm Immune Microenvironment

Filipe Reis Neves  1 , Ana Luís Martins  1 , Rui Caetano Oliveira  2 , Rui Martins  1   3
Affiliations
Review

Characterization of the Pancreatic Neuroendocrine Neoplasm Immune Microenvironment

Filipe Reis Neves et al. Cancer Med. 2025 Apr.

Abstract

Introduction: A tumor is composed of more than tumoral cells. In recent years, there has been an increase in interest and knowledge of the tumor microenvironment (TME).

Methods: The TME is an integral part of the tumor, composed of several cells: immune, stromal, and endothelial, among others, thus offering a wide range of tumor interactions and multiple possibilities for targeted therapies and environment modulation. While the TME in pancreatic ductal adenocarcinoma is widely studied, it is not very true for the TME of pancreatic neuroendocrine neoplasms (PNENs).

Discussion and conclusion: The incidence of PNENs is increasing and, therefore, it is important to comprehend their biology for the evolution of efficient therapies since many of the PNENs develop metastasis, including the G1 PNENs. This paper focuses on a review of the role of the TME in PNENs.

Keywords: immunotherapy; pancreatic cancer; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of angiogenesis in neuroendocrine tumors and the main molecular factors that regulate it (adapted from Yau, A.) [6].
FIGURE 2
FIGURE 2
A few types of cancer treatment available for cancer patients (adapted from Xiao, Y.) [12].
FIGURE 3
FIGURE 3
Schematic representation of the tumor immune microenvironment promoted by sEV piR‐hsa‐30937 in gastroenteropancreatic neuroendocrine tumors and the main factors that regulate it (adapted from Yao, AJ.) [47].
See this image and copyright information in PMC

References

    1. Chmiel P., Rychcik‐Pazyrska P., and Stec R., “Defining Tumor Microenvironment as a Possible Target for Effective GEP‐NENs Immunotherapy—A Systematic Review,” Cancers (Basel) 15, no. 21 (2023): 5232. - PMC - PubMed
    1. Yao J., Hassan M., Phan A., et al., “One Hundred Years After “Carcinoid”: Epidemiology of and Prognostic Factors for neuroendocrine Tumors in 35,825 Cases in the United States,” Journal of Clinical Oncology 26, no. 18 (2008): 3063–3072. - PubMed
    1. Raymond E., Dahan L., Raoul J., et al., “Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors,” New England Journal of Medicine 364 (2011): 501–513. - PubMed
    1. Yao J., Fazio N., Singh S., et al., “Everolimus for the Treatment of Advanced, Non‐Functional neuroendocrine Tumours of the Lung or Gastrointestinal Tract (RADIANT‐4): A Randomised, Placebo‐Controlled, Phase 3 Study,” Lancet 387, no. 10022 (2016): 968–977, 10.1016/S0140-6736(15)00817-X. - DOI - PMC - PubMed
    1. Anderson N. and Celeste M., “Tumor Microenvironment,” Current Biology 30, no. 16 (2020): R921–R925. - PMC - PubMed

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