Dataset related to article "Immune infiltrating cells in duodenal cancers"

This record contains data related to article "Immune infiltrating cells in duodenal cancers"

Abstract.

 Background: Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the

last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of

its biology, limiting the identification of tailored therapeutic options. A large body of evidence has clearly shown the

clinical relevance of immune cells in solid tumors, correlating immune features with post-surgical prognosis. The aim

of this study was to analyze the immune contexture in a cohort of duodenal adenocarcinomas surgically resected at

our Institution and define its correlation with clinical variables.

 Methods: Tissue slides from paraffin-embedded tumor specimens of 15 consecutive DA and 3 adenomas that

underwent a pancreaticoduodenectomy in our center between 2010 to 2018 were immunohistochemically stained.

The density (percentage of immune reactive area, IRA%) of immune markers CD45RO, CD8, CD20, IL-17, PD-1, CD68

was quantified by computer-assisted image analysis. Demographic, clinical, histopathological data were collected.

 Results: In our population, median IRA % (IQR) of immune subsets was respectively CD45RO-TILs 2.19 (2.14), CD8-TIL

0.42 (0.81), CD20-TILs 0.22 (0.51), CD20-TLT 2.84 (4.64), CD68-TAM 2.19 (1.56), IL17+

cells 0.39 (0.39), PD1-TILs 0.19 (0.41).

The median follow-up was 47.5 (22.4–63.3) months. At statistical analysis, the density of CD8-TILs inversely correlated

with lymph node ratio (p = 0.013), number of metastatic lymph nodes (p = 0.019), and was lower in N+ adenocarcinomas

compared to N0 (1.07 vs 0.29; p = 0.093), albeit not significantly. Stratifying patients for the N status, the density of

CD8-TILs decreased with the increasing of the N stage (p = 0.065) and was lower in patients who experienced recurrence

and died for the disease (0.276 vs 0.641; p = 0.044). Notably, also CD68-TAM distribution was different in patients

who had recurrence versus patients who did not (1.028 vs 2.276; p = 0.036).

 Conclusions: Immune cells showed variable expression in correlation with common prognostic factors, suggesting

T cell infiltration may play a protective role towards lymphatic spread of disease and nodal metastatization. Furthermore,

T cell density and macrophage infiltration were associated to a lower risk of recurrence and disease related

death. A multicentric approach may be indicated to allow analysis of larger cohorts of patients, potentially increasing

the power of our observations.

本数据集关联于论文《十二指肠癌中的免疫浸润细胞》。

## 摘要
### 研究背景
十二指肠腺癌（Duodenal Adenocarcinoma, DA）是一种罕见但极具侵袭性的恶性肿瘤，近数十年来其发病率呈上升趋势。由于该病发病率较低，学界对其发病机制与生物学特性的深入研究受到阻碍，也限制了个性化治疗方案的开发。大量研究已明确证实实体瘤中免疫细胞的临床相关性，且免疫特征与术后预后密切相关。本研究旨在分析本机构手术切除的十二指肠腺癌队列的免疫微环境，并明确其与临床变量的关联。

### 研究方法
本研究对2010年至2018年间在本中心接受胰十二指肠切除术的15例连续性十二指肠腺癌患者与3例腺瘤患者的石蜡包埋肿瘤标本组织切片进行免疫组织化学染色。通过计算机辅助图像分析，对CD45RO、CD8、CD20、IL-17、PD-1、CD68等免疫标志物的免疫反应区域占比（免疫反应面积百分比，immune reactive area, IRA%）进行定量检测。同时收集患者的人口统计学、临床及组织病理学数据。

### 研究结果
本研究队列中，各免疫亚群的IRA%中位数（四分位距）分别为：CD45RO阳性肿瘤浸润淋巴细胞（CD45RO-TILs）2.19（2.14）、CD8阳性肿瘤浸润淋巴细胞（CD8-TILs）0.42（0.81）、CD20阳性肿瘤浸润淋巴细胞（CD20-TILs）0.22（0.51）、CD20阳性三级淋巴组织（CD20-TLT）2.84（4.64）、CD68阳性肿瘤相关巨噬细胞（CD68-TAMs）2.19（1.56）、IL-17阳性细胞0.39（0.39）、PD-1阳性肿瘤浸润淋巴细胞（PD1-TILs）0.19（0.41）。
中位随访时间为47.5（22.4~63.3）个月。统计学分析显示，CD8-TILs密度与淋巴结比率（p=0.013）、转移淋巴结数量（p=0.019）呈负相关；淋巴结阳性（N+）腺癌患者的CD8-TILs密度低于淋巴结阴性（N0）患者（1.07 vs 0.29；p=0.093），虽未达到统计学显著性差异。按淋巴结状态对患者进行分层后可见，CD8-TILs密度随N分期升高呈下降趋势（p=0.065）；且出现复发及因该病死亡的患者CD8-TILs密度更低（0.276 vs 0.641；p=0.044）。值得注意的是，复发患者与未复发患者的CD68阳性肿瘤相关巨噬细胞分布存在显著差异（1.028 vs 2.276；p=0.036）。

### 研究结论
免疫细胞的表达水平与常见预后因素存在相关性，提示T细胞浸润可能对肿瘤淋巴扩散及淋巴结转移起到保护作用。此外，T细胞密度与巨噬细胞浸润水平与更低的复发风险及疾病相关死亡风险相关。未来可采用多中心研究方案，纳入更大规模的患者队列，以进一步提升本研究结论的统计效力。