Abstract
Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape immune response by impairing DC migration. Prostaglandin E2 (PGE2) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE2 could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXRα activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE2 rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE2 also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE2 treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape.
Highlights
Dendritic cells (DCs) are known as the most potent antigenpresenting cells at present and play a central role in tumorrelated immune response [1]
It was observed that the ability of DCs to initiate an immune response depends on their migration to draining lymph node [2] or immune escape could occur, which frequently is present in growing tumors such as prostate cancer (PCa) [3]
The addition of Prostaglandin E2 (PGE2) reversed this effect by decreasing ABCG1 and ABCA1 expressions and further expression of LXRα in DCs (Figure 1)
Summary
Dendritic cells (DCs) are known as the most potent antigenpresenting cells at present and play a central role in tumorrelated immune response [1]. Following various antigens such as tumor-associated antigen (TAA) uptake in the peripheral tissue, immature DCs mature and subsequently move to the secondary lymphoid tissue where they prime T cell response via presenting the antigenic peptides to T-lymphocytes in an MHC-restricted pattern. LXRβ is expressed ubiquitously, whereas LXRα has been detected in the liver, adipose tissue, adrenal glands, the intestine, the lungs, and cells of myelomonocytic lineage [6]. Studies have reported that LXRs can promote the elimination of apoptotic cells by DCs and macrophages, maintaining immune tolerance [8], and block the proliferation of T and Journal of Immunology Research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
