Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.36 (
hyaluronidase
)
4,606
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Highly accumulated hyaluronan (HA) not only provides a physiological barrier but also supports an immune-suppressive tumour microenvironment. High-molecular-weight (HMW)-HA inhibits the activation of immune cells and their access into tumour tissues, whereas, low-molecular-weight oligo-HA is known to potentially activate dendritic cells (DCs). In this paper, we investigated whether small extracellular vesicle (EVs)-PH20
hyaluronidase
induces tumour HA degradation, which, in turn, activates DCs to promote anti-cancer immune responses. Informed by our previous work, we used a small EV carrying GPI-anchored PH20
hyaluronidase
(Exo-PH20) that could deeply penetrate into tumour foci via HA degradation. We found that Exo-PH20-treatment successfully activates the maturation and migration of DCs
in vivo
, particularly
CD103
+
DCs leading to the activation of tumour-specific CD8
+
T cells, which work together to inhibit tumour growth. Moreover, combination with anti-PD-L1 antibody provided potent tumour-specific CD8
+
T cell immune responses as well as elicited prominent tumour growth inhibition both in syngenic and spontaneous breast cancer models, and this anti-tumour immunity was durable. Together, these results present new insights for HA degradation by Exo-PH20, providing a better understanding of oligo HA-triggered immune responses to cancer.
...
PMID:Degradation of tumour stromal hyaluronan by small extracellular vesicle-PH20 stimulates CD103
+
dendritic cells and in combination with PD-L1 blockade boosts anti-tumour immunity. 3163 19
