The role of IL‑17, IFN‑γ, 4‑1BBL and tumour‑infiltrating lymphocytes in the occurrence, development and prognosis of pancreatic cancer.

Abstract

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.