CD3+, CD8+, CD4+ and FOXP3+ T Cells in the Immune Microenvironment of Small Bowel Neuroendocrine Tumors.

Niko Hiltunen,Juha P Väyrynen,Olli Helminen,Jan Böhm

doi:10.3390/diseases9020042

Niko Hiltunen, Juha P Väyrynen + Show 2 more

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https://doi.org/10.3390/diseases9020042

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Abstract

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.

Highlights

Neuroendocrine tumors (NETs) are relatively rare neoplasms, developing in virtually any organ system from cells sharing a neural-endocrine phenotype [1]
The prognostic value of Immunoscore has been examined in other cancers, including pancreatic NETs, where the results suggest that a nomogram encompassing the Immunoscore system for pNETs (ISpnet) and patient-specific clinicopathological characteristics could effectively predict recurrence-free survival [10,11]
We found that densities of CD3+, CD8+, CD4+ and FOXP3+ T cells in SBNETs and Small bowel neuroendocrine tumors (SB-NETs) lymph node metastases were not significantly associated with disease-specific survival (DSS)

Summary

Introduction

Neuroendocrine tumors (NETs) are relatively rare neoplasms, developing in virtually any organ system from cells sharing a neural-endocrine phenotype [1]. Clinical presentation and prognosis of NETs vary significantly between different anatomic sites [2]. Among the most common NETs are gastroenteropancreatic NETs (GEP-NETs), which develop from the enteroendocrine cells of the gastrointestinal tract and pancreas [3]. Small bowel neuroendocrine tumors (SB-NETs) and gastric neuroendocrine tumors (G-NETs) are two separate entities within GEP-NETs. Based on data from the National Cancer Institute’s Surveillance, Epidemiology, and

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