Abstract
Programmed death ligand 1 (PD-L1), a type I transmembrane protein, binds to its receptor PD-1 to suppress the activation of T cells, thereby maintaining immunological homeostasis. In contrast, tumor cells highly express PD-L1, which binds to receptor PD-1 expressed on activated T cells, leading to immune escape. Anti-PD-1/PD-L1 immune checkpoint therapy blocks the binding of PD-1/PD-L1 to reinvigorate the exhausted T cells, thereby inhibiting tumor growth. Exosomes are biologically active lipid-bilayer nanovesicles secreted by various cell types that mediate intercellular signal communication. Numerous studies have shown that tumor cells are able to promote tumor epithelial-mesenchymal transition, angiogenesis, and immune escape by releasing exosomes. Recent studies imply that tumor-derived exosomes could carry PD-L1 in the same membrane topology as the cell surface, thereby resisting immune checkpoint therapy. In this review, we mainly discuss the role of exosomes in the regulation of tumor progression and the potential resistance mechanism to immunotherapy via exosomal PD-L1. In addition, we propose that exosomal PD-L1 may have the potential to be a target to overcome resistance to anti-PD-1/PD-L1 antibody therapy.
Highlights
Programmed death ligand 1 (PD-L1), known as cluster of differentiation 274 (CD274) or B7 homolog (B7 homolog 1, B7-H1), is a type I transmembrane protein of 290 amino acids encoded by the CD274 gene and consisting of immunoglobulin V-like and C-like extracellular domains [1]
The programmed death 1 (PD-1)/PD-L1 pathway plays a critical role in maintaining the balance between immunological tolerance and autoimmunity, but it can be a way for tumor cells to evade attacks by the host immune system
Tumor cells can deliver exosomes to different cell types to achieve the purposes of assimilation, including tumor cells, tumor mesenchymal cells, macrophages and dendritic cells (DCs)
Summary
Programmed death ligand 1 (PD-L1), known as cluster of differentiation 274 (CD274) or B7 homolog (B7 homolog 1, B7-H1), is a type I transmembrane protein of 290 amino acids encoded by the CD274 gene and consisting of immunoglobulin V-like and C-like extracellular domains [1]. We mainly discuss the role of exosomes in the regulation of tumor immunity and the potential resistance mechanism to immunotherapy via exosomes that express PD-L1 on their surface (the same membrane topology as cell surface PD-L1). Studies have reported that gastric cancer-derived exosomes can induce monocytes to differentiate into PD-1+ tumor-associated macrophages (TAMs), which can effectively suppress anti-tumor responses by triggering the PD-1/ PD-Ls signaling pathway [51].
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