免疫肿瘤微环境对胰腺和胃肠道神经内分泌肿瘤患者的预后意义。

Prognostic Implications of the Immune Tumor Microenvironment in Patients With Pancreatic and Gastrointestinal Neuroendocrine Tumors.

机构信息

From the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Department of Pathology, Johns Hopkins University.

出版信息

Pancreas. 2021;50(5):719-726. doi: 10.1097/MPA.0000000000001831.

DOI:10.1097/MPA.0000000000001831

PMID:34016898

Abstract

OBJECTIVES

The aim of this study was to characterize the tumor microenvironment of patients with gastroenteropancreatic neuroendocrine tumors relative to progression-free survival (PFS).

METHODS

Immune profiling for CD3, CD8, programmed death-1/programmed death-ligand 1, and indoleamine 2,3-dioxygenase expression in 2 cohorts of gastroenteropancreatic neuroendocrine tumors: patients with short PFS (<4 years, n = 12) versus long PFS (≥4 years, n = 14) after surgery. Immune infiltrates in the tumor and interface were quantified. Programmed death-ligand 1 expression was determined within the tumor, stroma, and interface.

RESULTS

Patients with shorter PFS had larger tumors (P = 0.02), mostly in the pancreas (P = 0.04). We observed a higher mean expression of CD3+, CD8+, programmed death-1+ cells, and indoleamine 2,3-dioxygenase at the interface compared with the tumor: log 10 mean differences 0.56 (95% confidence interval [CI], 0.43-0.68; P < 0.0001), 0.45 (95% CI, 0.32-0.59; P = 0.0002), 0.50 (95% CI, 0.40-0.61; P < 0.0001), and 0.24 (95% CI, 0.03-0.46; P = 0.046), respectively. Patients with longer PFS had higher intratumoral CD3+ T cells, log 10 mean difference 0.38 (95% CI, 0.19-0.57; P = 0.004). Programmed death-ligand 1 expression tended to be higher among patients with shortened PFS (odds ratio, 2.00; 95% CI, 0.68-5.91).

CONCLUSIONS

Higher intratumoral CD3+ T-cell infiltrate was associated with longer PFS after resection.

摘要

目的

本研究旨在分析胃肠胰神经内分泌肿瘤患者的肿瘤微环境与无进展生存期（progression-free survival，PFS）的关系。

方法

对 2 组胃肠胰神经内分泌肿瘤患者进行 CD3、CD8、程序性死亡受体 1（programmed death-1，PD-1）/程序性死亡配体 1（programmed death-ligand 1，PD-L1）和吲哚胺 2,3-双加氧酶（indoleamine 2,3-dioxygenase，IDO）免疫表型分析：手术治疗后 PFS 较短（<4 年，n=12）和较长（≥4 年，n=14）的患者。对肿瘤和界面处的免疫浸润进行定量分析。测定肿瘤、基质和界面内 PD-L1 的表达。

结果

PFS 较短的患者肿瘤较大（P=0.02），且主要位于胰腺（P=0.04）。与肿瘤相比，我们观察到界面处 CD3+、CD8+、PD-1+细胞和 IDO 的平均表达更高：log10 平均差异分别为 0.56（95%置信区间[confidence interval，CI]，0.43-0.68；P<0.0001）、0.45（95%CI，0.32-0.59；P=0.0002）、0.50（95%CI，0.40-0.61；P<0.0001）和 0.24（95%CI，0.03-0.46；P=0.046）。PFS 较长的患者肿瘤内 CD3+T 细胞较多，log10 平均差异为 0.38（95%CI，0.19-0.57；P=0.004）。PD-L1 的表达在 PFS 缩短的患者中趋于更高（比值比，2.00；95%CI，0.68-5.91）。