肿瘤免疫微环境对胰腺癌预后的影响：一项基于临床病理分析的回顾性研究

Impact of the tumor immune microenvironment on the outcome of pancreatic cancer: a retrospective study based on clinical pathological analysis.

作者信息

Huang Hui, Sun Jichun, Li Zhiqiang, Zhang Xianlin, Li Zheng, Zhu Hongwei, Yu Xiao

机构信息

Department of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.

Department of General Surgery, Affiliated Renhe Hospital of China, Three Gorges University, Yichang, China.

出版信息

Gland Surg. 2022 Feb;11(2):472-482. doi: 10.21037/gs-22-45.

DOI:10.21037/gs-22-45

PMID:35284302

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8899427/

Abstract

BACKGROUND

The cancerous microenvironment, characterized by the infiltration of CD4 and CD8 T cells, play a critical role in regulating the progression of cancer and treating efficiency of immunotherapy. However, the distribution of these cells and their associated cytokines in the tumor microenvironment of pancreatic cancer (PC) are not yet fully understood. Our study aims to analyze the contents of CD4IL-17 and CD8 T cells in PC and their relationship with the clinicopathological features and survival outcomes of patients.

METHODS

PC tissues and adjacent tissues were retrospectively collected from 40 patients in our hospital. The expression of CD4, IL-17, and CD8 in histological samples was measured by immunohistochemistry. The correlation between CD4, IL-17, and CD8 expression and clinical characteristics was analyzed using Kaplan-Meier survival analysis. The risk factors affecting the outcome of PC were examined by the Cox proportional hazards model, then a nomogram predicting the survival of PC using these risk factors was established.

RESULTS

The content of CD4IL-17 T cells in PC tissues was significantly higher than that in adjacent normal tissues, while the number of CD8 T cells was significantly lower than that in adjacent normal tissues (P<0.01). CD4 T cells in PC tissues was significantly associated with TNM stage and lymph node metastasis (P<0.05). IL-17 and CD8 were significantly associated with histological grade, TNM stage, local infiltration, and lymph node metastasis (P<0.05). The median survival times (MSTs) of CD4 positive and negative patients were 13.2 and 21.4 months, respectively. The MSTs of IL-17 positive and negative patients were 10.4 and 24.8 months, respectively. The MSTs were 21.9 and 11.8 months for CD8 positive and negative patients, respectively (P<0.05). The Cox regression model demonstrated that TNM staging, lymph node metastasis, and CD4IL-17 and CD8 T cells affected PC prognosis (P<0.05). The nomogram showed that the survival probability was reduced in patients with TNM stage III to IV, lymph node metastasis, high CD4IL-17 level, and low CD8 expression.

CONCLUSIONS

CD4IL-17 and CD8 T cells in PC tissues are associated with TNM staging, lymph node metastasis, and MST, and can be used as new prognostic indicators for PC.

摘要

背景

以CD4和CD8 T细胞浸润为特征的癌微环境在调节癌症进展和免疫治疗疗效方面起着关键作用。然而，这些细胞及其相关细胞因子在胰腺癌（PC）肿瘤微环境中的分布尚未完全明确。我们的研究旨在分析PC中CD4⁺IL-17和CD8 T细胞的含量及其与患者临床病理特征和生存结局的关系。

方法

回顾性收集我院40例患者的PC组织和癌旁组织。采用免疫组织化学法检测组织学样本中CD4、IL-17和CD8的表达。采用Kaplan-Meier生存分析法分析CD4、IL-17和CD8表达与临床特征之间的相关性。通过Cox比例风险模型检测影响PC预后的危险因素，然后建立使用这些危险因素预测PC生存的列线图。

结果

PC组织中CD4⁺IL-17 T细胞含量显著高于癌旁正常组织，而CD8 T细胞数量显著低于癌旁正常组织（P<0.01）。PC组织中的CD4 T细胞与TNM分期和淋巴结转移显著相关（P<0.05）。IL-17和CD8与组织学分级、TNM分期、局部浸润和淋巴结转移显著相关（P<0.05）。CD4阳性和阴性患者的中位生存时间（MST）分别为13.2个月和21.4个月。IL-17阳性和阴性患者的MST分别为10.4个月和24.8个月。CD8阳性和阴性患者的MST分别为21.9个月和11.8个月（P<0.05）。Cox回归模型显示，TNM分期、淋巴结转移以及CD4⁺IL-17和CD8 T细胞影响PC预后（P<0.05）。列线图显示，TNM III至IV期、淋巴结转移、CD4⁺IL-17水平高且CD8表达低的患者生存概率降低。