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Published on: April 18, 2016
Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation
Yves Delneste1, Giovanni Magistrelli, Jean Gauchat
1Centre d'Immunologie Pierre Fabre, 5 avenue Napoléon III, Saint Julien en Genevois, France.
Insights
Scavenger receptors, particularly LOX-1, facilitate antigen uptake by dendritic cells for cross-priming. Targeting LOX-1 with tumor antigens can induce antitumor immunity, showing its promise in cancer immunotherapy.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Cross-priming initiates T-cell responses via MHC class I pathway.
- Dendritic cell receptors for antigen endocytosis in cross-priming are largely unidentified.
Purpose of the Study:
- Identify receptors responsible for heat shock protein (HSP) uptake by dendritic cells.
- Investigate the role of identified receptors in antigen cross-presentation and anti-tumor immunity.
Main Methods:
- Utilized human dendritic cells to study scavenger receptor binding of HSPs.
- Employed neutralizing anti-LOX-1 monoclonal antibodies (mAbs) to assess LOX-1 function.
- Evaluated in vivo anti-tumor immune responses following LOX-1 targeting.
Main Results:
- Scavenger receptors are the primary HSP-binding structures on human dendritic cells.
- LOX-1 was identified as a key scavenger receptor involved in HSP binding.
- Anti-LOX-1 mAb inhibited HSP70 binding and subsequent antigen cross-presentation.
- Targeting LOX-1 with tumor antigens in vivo successfully induced anti-tumor immunity.
Conclusions:
- LOX-1 is a crucial scavenger receptor for HSP uptake and antigen cross-presentation by dendritic cells.
- LOX-1 represents a promising therapeutic target for developing novel cancer immunotherapies.
Abstract:
Some exogenous antigens, such as heat shock proteins or apoptotic bodies, gain access to the MHC class I processing pathway and initiate CTL responses, a process called cross-priming. To be efficient in vivo, this process requires endocytosis of the antigen by dendritic cells via receptors which remain unidentified. Here, we report that scavenger receptors are the main HSP binding structures on human dendritic cells and identify LOX-1 as one of these molecules. A neutralizing anti-LOX-1 mAb inhibits Hsp70 binding to dendritic cells and Hsp70-induced antigen cross-presentation. In vivo, to target LOX-1 with a tumor antigen using an anti-LOX-1 mAb induces antitumor immunity. Thus, the scavenger receptor LOX-1 is certainly a promising target for cancer immunotherapy.
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