Liu Yingying, Zhang Ke, Cai Xiaodi, Zhou Jikai, Cai Yixuan, Gu Yujie, Xia Tingting, Ye Jianxin
Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214000, P.R. China.
Department of Gastroenterology, Affiliated Changshu Hospital of Nantong University, Changshu, Jiangsu 215500, P.R. China.
Oncol Lett. 2024 Dec 5;29(2):88. doi: 10.3892/ol.2024.14834. eCollection 2025 Feb.
Immunotherapy has made progress in the treatment of tumours; however, in patients with pancreatic cancer, immunotherapy has not achieved effective results. The present study investigated changes in the immune microenvironment during tumour development and progression, and the relationship between the immune microenvironment and prognosis, to clarify the mechanism of immune escape in pancreatic cancer. A total of 40 patients with pancreatic cancer (including 22 with stage I-II disease and 18 with stage III-IV disease) and 20 patients with chronic pancreatitis were included in the present study. The expression of CD3, CD4, CD8, CD56, IFN-γ, IL-17 and 4-1BBL was assessed by immunohistochemistry, and the mRNA expression levels were detected by reverse transcription-quantitative PCR (RT-qPCR). The clinicopathological characteristics and prognoses of patients with pancreatic cancer were analysed to further explore the role of IL-17, IFN-γ, 4-1BBL and tumour-infiltrating lymphocytes in pancreatic cancer. Notably, the expression levels of CD3, CD8, CD56, IFN-γ and 4-1BBL in patients with stages I-II and III-IV cancer were lower than those in patients with chronic pancreatitis (P<0.05), especially in patients with stage III-IV cancer (P<0.05). In addition, the expression of IL-17 in patients with stages I-II and III-IV cancer was greater than in patients with chronic pancreatitis (P<0.05), especially in patients with stage III-IV cancer (P<0.05). The RT-qPCR results regarding CD3, CD4, CD8, CD56, IFN-γ and IL-17 were almost the same as those obtained from immunohistochemical analysis; however, the mRNA expression levels of 4-1BBL were not significantly different between stages I-II and III-IV. Furthermore, patients with pancreatic cancer with higher expression levels of CD3, CD8, CD56, IFN-γ and 4-1BBL exhibited longer survival, whereas those with higher expression of IL-17 had a shorter survival time. The expression levels of CD3, CD8, CD56, cytokines IL-17 and IFN-γ, and costimulatory molecule 4-1BBL were revealed to be related to the degree of differentiation, Tumour-Node-Metastasis staging and the prognosis of pancreatic cancer, and may serve as novel immunological indicators for evaluating the condition and treatment effectiveness in patients with pancreatic cancer.
免疫疗法在肿瘤治疗方面取得了进展；然而，在胰腺癌患者中，免疫疗法尚未取得有效成果。本研究调查了肿瘤发生发展过程中免疫微环境的变化，以及免疫微环境与预后的关系，以阐明胰腺癌免疫逃逸的机制。本研究共纳入40例胰腺癌患者（包括22例I-II期患者和18例III-IV期患者）和20例慢性胰腺炎患者。通过免疫组织化学评估CD3、CD4、CD8、CD56、IFN-γ、IL-17和4-1BBL的表达，并通过逆转录定量PCR（RT-qPCR）检测mRNA表达水平。分析胰腺癌患者的临床病理特征和预后，以进一步探讨IL-17、IFN-γ、4-1BBL和肿瘤浸润淋巴细胞在胰腺癌中的作用。值得注意的是，I-II期和III-IV期癌症患者的CD3、CD8、CD56、IFN-γ和4-1BBL表达水平低于慢性胰腺炎患者（P<0.05），尤其是III-IV期癌症患者（P<0.05）。此外，I-II期和III-IV期癌症患者的IL-17表达高于慢性胰腺炎患者（P<0.05），尤其是III-IV期癌症患者（P<0.05）。关于CD3、CD4、CD8、CD56、IFN-γ和IL-17的RT-qPCR结果与免疫组织化学分析结果几乎相同；然而，I-II期和III-IV期之间4-1BBL的mRNA表达水平无显著差异。此外，CD3、CD8、CD56、IFN-γ和4-1BBL表达水平较高的胰腺癌患者生存期较长，而IL-17表达较高的患者生存期较短。CD3、CD8、CD56、细胞因子IL-17和IFN-γ以及共刺激分子4-1BBL的表达水平与胰腺癌的分化程度、肿瘤-淋巴结-转移分期及预后相关，可能作为评估胰腺癌患者病情及治疗效果的新型免疫指标。
