PD-L1-Expressed Exosome Modification Service

PD-L1 (Programmed death-ligand 1) is an essential immunomodulatory molecule, and its high expression is frequently a survival strategy to evade phagocytosis in conditions such as tumors and inflammation. The biological role played by PD-L1 in exosomes remains to be explored in depth, with the potential to prolong the circulation of exosomes by evading phagocytosis. Creative Biolabs offers PD-L1-expressed exosome modification services to explore the potential for improving the performance of exosome delivery platforms.

PD-L1/PD-1 Pathway Mediates Evasion of Phagocytosis

PD-L1 is a regulatory molecule of the body's immune function and is one of the immune regulatory ligands of PD-1 (Programmed death 1). The PD-1/PD-L1 pathway is involved in regulating the regular immune system as well as an important mechanism of immune escape states such as tumor and inflammation. On the one hand, PD-L1 regulates adaptive immune responses by binding PD-1 on the surface of T lymphocytes, including inhibiting the activation of T cells and inducing their apoptosis so that immune cells lose the ability to attack tumor cells or inflammatory cells. On the other hand, it has been found that the level of expressed PD-1 on TAMs (tumor-associated macrophages) is also negatively correlated with their phagocytosis. And blockade of PD-1/PD-L1 increased phagocytosis of TAMs and induced an antitumor effect of innate immunity, showing TAM-dependent prolongation of survival in mice with disease models. The above evidence suggests that PD-L1 could be an exciting candidate molecule to confer the ability of exosomes to evade cytophagy.

Fig.1 PD-L1 binding to PD-1 reduces phagocytic activity. (Marchetti, 2017)

Modification of PD-L1-Expressed Exosomes

There has been demonstrated that the PD-1/PD-L1 pathway mediates the inhibition of TAMs and T-cell immunity against tumor cells. Therefore, modification of PD-L1 on the surface of exosomes by engineering modifications is a promising strategy to inhibit phagocytosis of exosomes by macrophages. On the one hand, PD-L1-expressing exosomes have been found to be potentially generated in tumor cells, immune cells, MSCs, and tumor microenvironments with specific signaling roles that distinguish them from exosomes of other cellular origins. On the other hand, PD-L1-expressing exosomes can also be generated by transfection of PD-L1-containing expression plasmids to modify specific donor cells or surface-modified PD-L1 ligands. Based on previous evidence that PD-L1 inhibits phagocytosis of TAMs and to some extent can also interact to enhance immunosuppressive effects, the alteration of phagocyte recognition and catabolism by PD-L1-expressing exosomes can be monitored by cellular uptake assays and intratumoral targeted retention assays, thus explore whether this modification strategy contributes to prolonged exosome recycling.

Fig.2 Isolation of different forms of soluble (extracellular) PD-L1. (Daassi, 2020)

PD-L1 signaling inhibits the innate immune response through a negative effect on the phagocytosis of TAMs opening new directions for improving the potential of exosome-targeted delivery. Moreover, the mechanisms related to the anti-phagocytosis effect of exosomes need to be further investigated. At Creative Biolabs, we have developed a variety of exosome engineering strategies that can provide services for the modification of PD-L1-expressed exosomes and the research of their phagocytosis-evading related mechanisms, thus helping our customers to advance the research of exosome vector-based therapeutic systems. Please contact us to discuss your project.

References

Marchetti, A.; et al. Why anti-PD1/PDL1 therapy is so effective? Another piece in the puzzle. J Thorac Dis. 2017, 9(12): 4863-4866.
Daassi, D.; et al. The importance of exosomal PDL1 in tumour immune evasion. Nat Rev Immunol. 2020, 20(4): 209-215.

Plant Exosome Isolation