免疫调节性叉头框蛋白p3阳性淋巴细胞与胰腺神经内分泌肿瘤患者的总生存期相关。

Immunoregulatory Forkhead Box Protein p3-Positive Lymphocytes Are Associated with Overall Survival in Patients with Pancreatic Neuroendocrine Tumors.

作者信息

de Reuver Philip R, Mehta Shreya, Gill Preetjote, Andrici Juliana, D'Urso Lisa, Clarkson Adele, Mittal Anubhav, Hugh Thomas J, Samra Jaswinder S, Gill Anthony J

机构信息

Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, New South Wales, Australia.

出版信息

J Am Coll Surg. 2016 Mar;222(3):281-7. doi: 10.1016/j.jamcollsurg.2015.12.008. Epub 2015 Dec 18.

DOI:10.1016/j.jamcollsurg.2015.12.008

PMID:26809747

Abstract

BACKGROUND

Forkhead box protein p3-positive (FoxP3(+)) regulatory T cells (Tregs) suppress host T-cell-mediated immune responses, limit surveillance against cancers, and have been associated with a poor prognosis.

STUDY DESIGN

This study aims to identify the prognostic significance of FoxP3(+) Tregs in pancreatic neuroendocrine tumors (PNETs). Patients diagnosed with PNETs between 1992 and 2014 (n = 101) were included in this retrospective analysis. Clinical data, histopathology, and expression of FoxP3(+) Tregs and Ki-67 by immunohistochemistry were assessed. The association of these factors with survival was tested by log-rank test and in additional multivariable analysis.

RESULTS

A total of 101 patients were included in this study. Mean age was 58.0 years (range 18 to 87 years) and median tumor size was 25 mm (range 8 to 160 mm). The degree of infiltration of tumor by FoxP3(+) Tregs was graded as 0 (n = 75), 1 (n = 15), or 2 (n = 11). Median follow-up was 50 months (interquartile range 123 months; Q1 = 20 months and Q3 = 123 months). In univariate analyses, patient age older than 57 years, TNM stage III or IV, tumor size >25 mm, Ki-67 labeling index >20, and a high number of FoxP3(+) tumor-infiltrating lymphocytes were significantly associated with poorer overall survival. In multivariable analyses, FoxP3(+) expression score of 2 (hazard ratio = 6.9; 95% CI 1.4-34.4) was the only statistically significant predictor for overall mortality.

CONCLUSIONS

FoxP3(+) Treg expression is an independent prognostic factor in patients with PNETs, associated with statistically significant shorter overall survival. There is a role for additional research into the immune-mediated role of FoxP3(+) Tregs in PNETs.

摘要

背景

叉头框蛋白p3阳性（FoxP3(+)）调节性T细胞（Tregs）可抑制宿主T细胞介导的免疫反应，限制对癌症的监测，且与预后不良相关。

研究设计

本研究旨在确定FoxP3(+) Tregs在胰腺神经内分泌肿瘤（PNETs）中的预后意义。本回顾性分析纳入了1992年至2014年间诊断为PNETs的患者（n = 101）。评估了临床数据、组织病理学以及通过免疫组织化学检测的FoxP3(+) Tregs和Ki-67的表达。通过对数秩检验以及额外的多变量分析来检验这些因素与生存的相关性。

结果

本研究共纳入101例患者。平均年龄为58.0岁（范围18至87岁），肿瘤中位大小为25 mm（范围8至160 mm）。FoxP3(+) Tregs对肿瘤的浸润程度分为0级（n = 75）、1级（n = 15）或2级（n = 11）。中位随访时间为50个月（四分位间距123个月；Q1 = 20个月，Q3 = 123个月）。在单变量分析中，年龄大于57岁、TNM分期为III或IV期、肿瘤大小>25 mm、Ki-67标记指数>20以及大量FoxP3(+)肿瘤浸润淋巴细胞与较差的总生存期显著相关。在多变量分析中，FoxP3(+)表达评分为2（风险比 = 6.9；95% CI 1.4 - 34.4）是总死亡率的唯一具有统计学意义的预测因素。