TIM-4 increases the proportion of CD4 + CD25 + FOXP3 + regulatory T cells in the pancreatic ductal adenocarcinoma microenvironment by inhibiting IL-6 secretion.

Autor: Wang Z; Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China., Xie Z; Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.; Department of General Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China., Mou Y; Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China., Geng R; Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China., Chen C; Department of Radiology, The First People's Hospital of Chengdu, Chengdu, China., Ke N; Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2024 Sep; Vol. 13 (17), pp. e70110.
DOI: 10.1002/cam4.70110
Abstrakt: Background: Currently, creating more effector T cells and augmenting their functions is a focal point in pancreatic ductal adenocarcinoma (PDAC) treatment research. T cell immunoglobulin domain and mucin domain molecule 4 (TIM-4), known for promoting cancer progression in various malignancies, is implicated in the suppressive immune microenvironment of tumors. Analyzing of the role of TIM-4 in the immune regulation of PDAC can offer novel insights for immune therapy.
Methods: We analyzed the TIM-4 expression in tumor specimens from PDAC patients. Meanwhile, multiple fluorescent immunohistochemical staining was used to study the distribution characteristics of TIM-4, and through tissue microarrays, we explored its correlation with patient prognosis. The influence of TIM-4 overexpression on cell function was analyzed using RNA-seq. Flow cytometry and ELISA were used for verification. Finally, the relationship between TIM-4 and T lymphocytes was analyzed by tissue microarray, and the impacts of TIM-4 on T cell subsets were observed by cell coculture technology and a mouse pancreatic cancer in situ model.
Results: In PDAC, TIM-4 is mainly expressed in tumor cells and negatively correlated with patient prognosis. TIM-4 influences the differentiation of Treg by inhibiting IL-6 secretion in pancreatic cancer cells and facilitates the proliferation of pancreatic cancer in mice. Additionally, the mechanism may be through the CD8 + effector T cells (CD8 + Tc).
Conclusion: TIM-4 has the potential to be an immunotherapeutic target or to improve the efficacy of chemotherapy for PDAC.
(© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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