DPP4 promotes an immunoenhancing tumor microenvironment through exhausted CD8+ T cells with activating IL13-IL13RA2 axis in papillary thyroid cancer.

Autor: Jing R; Department of Breast and Thyroid Surgery, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, PR China., Wu N; Department of Breast and Thyroid Surgery, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China., Zhang Q; Respiratory Medicine, Shenzhen Pingle Orthopedic Hospital (Shenzhen Pingshan Traditional Chinese Medicine Hospital), Shenzhen 518118, PR China., Liu J; Department of Clinical Laboratory, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China., Zhao Y; Department of Clinical Laboratory, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China., Zeng S; Department of Pathology, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China., Wu S; Department of Breast and Thyroid Surgery, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China., Wu Y; Department of Breast and Thyroid Surgery, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China. Electronic address: szwy1022@163.com., Yi S; Department of Breast and Thyroid Surgery, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China. Electronic address: yishijian1969@szu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2025 Jan 03; Vol. 145, pp. 113760. Date of Electronic Publication: 2024 Dec 10.
DOI: 10.1016/j.intimp.2024.113760
Abstrakt: Background: Papillary thyroid cancer (PTC) is among the most prevalent forms of endocrine malignancy with a rapid rise in incidence rates worldwide; however, the composition and characteristics of its immune microenvironment is poorly understand. Here, this work investigated the precise function of Dipeptidyl peptidase 4 (DPP4) in tumor-infiltrated T cells within PTC by investigating its role in cytokine-mediated signaling pathways.
Methods: TCGA and GEO data as well as human PTC specimens confirmed the expression of DPP4 in PTC. The CIBERSORT and TIMER tool were used to analyze the distribution of tumor-infiltrating immune cells in PTC. CD8+ T cells from PTC patient's peripheral blood were cultured and used in a three-dimensional model for direct co-culture with PTC tumors to investigate DPP4 function.
Results: Bioinformatic analyses has uncovered a significant upregulation of DPP4, which enhances the survival and migration of PTC cells in vitro. DPP4 upregulation significantly correlated with advanced grades, stages, and poor progression-free survival. DPP4 influences immune function and the exhaustion of CD8+ T cells through the IL13-IL13RA2 axis. The inhibition of DPP4 reduces CD8+ T cell exhaustion and IL13 secretion, while also blocking the IL13-IL13RA2 axis, thereby promoting the mesenchymal-to-epithelial transition of PTC cells.
Conclusion: Blocking DPP4 leads to the conversion of exhausted CD8+ T cells with decreased IL13 level, resulting in downregulation of IL13RA2 to promote mesenchymal-to-epithelial transition of PTC cells. This highlights DPP4 as a potential therapeutic target, particularly between CD8+ T cells and PTC cells via IL13-IL13RA2 axis, and represents a novel avenue for combined immunotherapy in PTC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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