Implications of PD-1, Tim-3, and TIGIT Expression for Cancer Immunity and Pancreatic Cancer Prognosis

Abstract

Background/aim: The development and application of cancer immunotherapy to pancreatic cancer has not progressed because its efficacy has not been proven in clinical trials. In this study, we aimed to explore potential targets of immune checkpoint inhibitor therapy for pancreatic cancer treatment.

Materials and methods: We collected resected specimens from 40 patients with pancreatic cancer who underwent resection at our Institution without any preoperative treatment. We evaluated the expression of molecules in the programmed death receptor-1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3)/Galectin-9, and CD155/T cell immunoreceptor with Ig and ITIM domains (TIGIT) pathways using immunohistochemical staining. The correlation between the expression pattern of these molecules and patient prognosis were assessed using Kaplan-Meier analysis.

Results: An increased number of CD8⁺ T cells in pancreatic cancer tissue was significantly associated with a better patient prognosis. Additionally, patients with a higher ratio of PD-1 expression to CD8⁺ T cells had a worse prognosis. We observed no correlation between the Tim-3/Galectin-9 and CD155/TIGIT pathways and patient prognosis.

Conclusion: Modifications in the immune environment to increase T cell infiltration into tumors could result in the PD-1 pathway becoming a potential target to treat pancreatic cancer using immune checkpoint inhibition.

Keywords: CD155; Cancer immunity; PD-1; PD-L1; PD-L2; TIGIT; Tim-3; galectin-9; pancreatic cancer.