University of Oulu

Hiltunen, N.; Väyrynen, J.P.; Böhm, J.; Helminen, O. CD3+, CD8+, CD4+ and FOXP3+ T Cells in the Immune Microenvironment of Small Bowel Neuroendocrine Tumors. Diseases 2021, 9, 42.

CD3⁺, CD8⁺, CD4⁺ and FOXP3⁺ T cells in the immune microenvironment of small bowel neuroendocrine tumors

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Author: Hiltunen, Niko1; Väyrynen, Juha P.1,2; Böhm, Jan2;
Organizations: 1Cancer and Translational Medicine Research Unit, Medical Research Center, University of Oulu, Oulu University Hospital, 90220 Oulu, Finland
2Department of Pathology, Central Finland Central Hospital, 40620 Jyväskylä, Finland
3Surgery Research Unit, Medical Research Center, University of Oulu, Oulu University Hospital, 90220 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 20.4 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-10-11


The role of inflammation in neuroendocrine tumors is poorly known. The purpose of this study was to characterize the densities of CD3⁺, CD8⁺, CD4⁺ and FOXP3⁺ T cells in small bowel neuroendocrine tumors (SB-NETs), SB-NET lymph node metastases and gastric neuroendocrine tumors (G-NETs) to assess the prognostic role of immune cell infiltrates in SB-NETs. The final cohort included 113 SB-NETs, 75 SB-NET lymph node metastases and 19 G-NETs from two Finnish hospitals. CD3⁺- and CD8⁺-based immune cell score (ICS), and other T cell densities were evaluated. Survival analyses of SB-NETs and SB-NET lymph node metastases were performed with the Kaplan-Meier method and Cox regression adjusted for confounders. The primary outcome was disease-specific survival (DSS). No significant difference in DSS was seen between low and high ICS groups in SB-NETs at 5 years (92.6% vs. 87.8%) or 10 years (53.8% vs. 79.4%), p = 0.507, or in SB-NET lymph node metastases at 5 years (88.9% vs. 90.4%) or 10 years (71.1% vs. 59.8%), p = 0.466. Individual densities of the examined T cell types showed no correlation with prognosis either. SB-NETs and lymph node metastases had similar inflammatory cell profiles, whereas in G-NETs CD3⁺ and CD8⁺ T cells were particularly more abundant. In SB-NETs, ICS or T cell densities showed no correlation with prognosis.

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Series: Diseases
ISSN: 2079-9721
ISSN-E: 2079-9721
ISSN-L: 2079-9721
Volume: 9
Issue: 2
Article number: 42
DOI: 10.3390/diseases9020042
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This study was funded by the Instrumentarium Science Foundation (O.H.), Mary and Georg C. Ehrnrooth Foundation (O.H.) and Finnish State Research Funding (J.B. and O.H.).
Copyright information: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (