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- Title
OX40L enhances the immunogenicity of dendritic cells and inhibits tumor metastasis in mice.
- Authors
Zhao, Lin; Zhang, Wenjie; Liu, Meng; Jia, Ruoyu; Wang, Juncheng; Wang, Fengge; Xu, Yuekang
- Abstract
A well preserved immune system is a powerful tool to prevent foreign invasion or to suppress internal mutation, which must be tightly controlled by co‐stimulatory molecules in different pathophysiological conditions. One such critical molecule is OX40L expressed on activated antigen‐presenting cells (APCs). Consistently, its abnormality is associated with various immunological disorders such as autoinflammatory diseases and allergy. However, a comprehensive analysis of the immune‐moderating role of OX40L in dendritic cells (DCs), the most powerful APCs to initiate immune responses in vivo, and investigation of its anti‐tumor efficacy in the disease setting have not been performed properly. In this study, genetic approaches for both gain‐of‐function and reduction‐of‐function were employed to reveal that OX40L was required for the efficient presentation, but not uptake, of antigens by DCs to stimulate CD4+, as well as CD8+ T cells in vivo. As a result, CD4+ T cells were promoted towards Th1, but inhibited on Treg differentiation, by the LPS‐induced OX40L on DCs, which was supported by their altered expression of co‐inhibitory receptor, PD‐L1. CD8+ T cells, on the other hand, also enhanced their cytotoxicity towards target cells in response to OX40L expression on the DCs transferred in vivo. Finally, in a DC‐mediated tumor immunity model, the strong immunogenic roles of OX40L on DCs led to better metastasis inhibition in vivo. Collectively, our results demonstrate that OX40L could serve as a potential target in the DC‐based vaccine for enhanced anti‐tumor efficacy in vivo.
- Subjects
DENDRITIC cells; IMMUNE response; METASTASIS; T cells; AUTOINFLAMMATORY diseases; PROGRAMMED cell death 1 receptors
- Publication
Microbiology & Immunology, 2023, Vol 67, Issue 2, p79
- ISSN
0385-5600
- Publication type
Article
- DOI
10.1111/1348-0421.13037