ZG16 enhances the maturation of dendritic cells via induction of CD40 and contributes to the antitumor immunity in pancreatic cancer

Hui Meng ¹, Ling Li ², Manman Nan ³

⁰Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China. menghui2000@zzu.edu.cn.

Oncogene +

|

September 11, 2024

View abstract on PubMed

Summary

Zymogen granule protein 16 (ZG16) promotes dendritic cell (DC) maturation and pancreatic cancer immunotherapy by stabilizing CD40. Recombinant ZG16 protein enhances anti-tumor responses and synergizes with gemcitabine.

Area Of Science

Immunology
Oncology
Cell Biology

Background

Dendritic cells (DCs) are crucial for initiating T-cell responses against tumors.
Zymogen granule protein 16 (ZG16) has shown anti-oncogene properties, but its role in DC function is unclear.
Understanding ZG16's impact on DCs is vital for developing novel pancreatic cancer immunotherapies.

Purpose Of The Study

To investigate the effect of ZG16 on dendritic cell activation and maturation.
To explore the potential of ZG16 as a therapeutic agent for pancreatic cancer.
To elucidate the molecular mechanism underlying ZG16's function in DC-based immunotherapy.

Main Methods

Analyzed ZG16 expression during DC maturation.
Overexpressed ZG16 or administered recombinant ZG16 protein to DCs.
Utilized subcutaneous and orthotopic mouse models of pancreatic cancer.
Investigated the interaction between ZG16 and CD40 via ubiquitination assays.

Main Results

ZG16 expression increased during DC maturation.
ZG16 enhanced DC maturation markers (MHC II, CD86, CD84, CCR7) and pro-inflammatory cytokines.
Recombinant ZG16 protein (Re-mZG16) induced tumor regression and boosted anti-tumor T-cell responses in mouse models.
Re-mZG16 showed synergistic effects with gemcitabine in pancreatic cancer treatment.
ZG16 inhibited CD40 ubiquitination and degradation, dependent on its lectin domain.

Conclusions

ZG16 promotes dendritic cell maturation and enhances anti-tumor immunity.
The ZG16-CD40 axis is a key mechanism in ZG16-mediated DC immunotherapy for pancreatic cancer.
ZG16 represents a promising target for developing novel immunotherapies against pancreatic cancer.

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