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
- Authors
- Hong, Yeonsun; Kim, Yoon Kyoung; Kim, Gi Beom; Nam, Gi-Noon; Kim, Seong A.; Park, Yoon; Yang, Yoosoo; Kim, In-San
- Issue Date
- 1-12월-2019
- Publisher
- TAYLOR & FRANCIS LTD
- Keywords
- Extracellular vesicle; hyaluronidase; dendritic cell; cancer immunotherapy; hyaluronan; immune checkpoint blockade
- Citation
- JOURNAL OF EXTRACELLULAR VESICLES, v.8, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF EXTRACELLULAR VESICLES
- Volume
- 8
- Number
- 1
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/60987
- DOI
- 10.1080/20013078.2019.1670893
- ISSN
- 2001-3078
- Abstract
- 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.
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Collections - Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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