Hong, Yeonsun Kim, Yoon Kyoung Kim, Gi Beom Nam, Gi-Noon Kim, Seong A. Park, Yoon Yang, Yoosoo Kim, In-San 2024-01-19T18:33:19Z 2024-01-19T18:33:19Z 2022-01-10 2019-12 2001-3078 https://pubs.kist.re.kr/handle/201004/119243 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. English Co-Action Publishing 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 Article 10.1080/20013078.2019.1670893 1 Journal of Extracellular Vesicles, v.8, no.1 Journal of Extracellular Vesicles 8 1 Y scie scopus 000487921100001 2-s2.0-85073213859 Cell Biology Cell Biology Article ASSISTED CARBOHYDRATE ELECTROPHORESIS TOLL-LIKE RECEPTOR NF-KAPPA-B SIGNAL-TRANSDUCTION CANCER PROGRESSION MICROENVIRONMENT IMMUNOTHERAPY OLIGOSACCHARIDES INFILTRATION EXPRESSION Extracellular vesicle hyaluronidase dendritic cell cancer immunotherapy hyaluronan immune checkpoint blockade