Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice

Abstract As a type of “cold tumor” with limited immune cell infiltration, ovarian cancer has historically shown limited efficacy in immunotherapy. In this study, we report that exosomes from ovarian cancer can specifically target omentum which is the predilection site for ovarian cancer to metastasi...

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Main Authors: Yuanyuan Wang, Changyi Zhang, Huimin Zeng, Liangliang Wang, Zanhong Wang, Zhiqiang Han
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Cancer Immunology, Immunotherapy
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Online Access:https://doi.org/10.1007/s00262-025-03951-2
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author Yuanyuan Wang
Changyi Zhang
Huimin Zeng
Liangliang Wang
Zanhong Wang
Zhiqiang Han
author_facet Yuanyuan Wang
Changyi Zhang
Huimin Zeng
Liangliang Wang
Zanhong Wang
Zhiqiang Han
author_sort Yuanyuan Wang
collection DOAJ
description Abstract As a type of “cold tumor” with limited immune cell infiltration, ovarian cancer has historically shown limited efficacy in immunotherapy. In this study, we report that exosomes from ovarian cancer can specifically target omentum which is the predilection site for ovarian cancer to metastasize and combat subsequently implanted tumor. Furthermore, we found a substantial increase in the proportion of CD3 + T cells, particularly CD8 + T cells, within the omental tissue where exosomes homed. This increase was accompanied by a significant enhancement in granzyme B levels within CD8 + T cells. Additionally, there was a notable elevation in the concentration of interferon-gamma (IFN-γ) in peripheral blood. In vitro results indicated that exosomes could be internalized by dendritic cells (DCs), promote DC differentiation, and subsequently induce the production of granzyme B and IFN-γ in T cells. Surprisingly, we also observed high expression of programmed death ligand 1 (PD-L1) in the omentum. Therefore, we discovered whether combining PD-L1 blockade led to further tumor regression. However, although the combination group showed complete tumor regression, this difference did not reach statistical significance. But in general, we emphasize that in the case of pre-injection, exosomes have great potential to combat the famous “cold tumor”, ovarian cancer, via targeting omentum and activating anti-tumor immunity, offering a novel avenue for overcoming ovarian cancer.
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publishDate 2025-02-01
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series Cancer Immunology, Immunotherapy
spelling doaj-art-bc64c2c34ce24a8b8d9ec56fe8daa7cb2025-02-09T12:39:11ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-0174311210.1007/s00262-025-03951-2Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in miceYuanyuan Wang0Changyi Zhang1Huimin Zeng2Liangliang Wang3Zanhong Wang4Zhiqiang Han5Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical UniversityDepartment of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract As a type of “cold tumor” with limited immune cell infiltration, ovarian cancer has historically shown limited efficacy in immunotherapy. In this study, we report that exosomes from ovarian cancer can specifically target omentum which is the predilection site for ovarian cancer to metastasize and combat subsequently implanted tumor. Furthermore, we found a substantial increase in the proportion of CD3 + T cells, particularly CD8 + T cells, within the omental tissue where exosomes homed. This increase was accompanied by a significant enhancement in granzyme B levels within CD8 + T cells. Additionally, there was a notable elevation in the concentration of interferon-gamma (IFN-γ) in peripheral blood. In vitro results indicated that exosomes could be internalized by dendritic cells (DCs), promote DC differentiation, and subsequently induce the production of granzyme B and IFN-γ in T cells. Surprisingly, we also observed high expression of programmed death ligand 1 (PD-L1) in the omentum. Therefore, we discovered whether combining PD-L1 blockade led to further tumor regression. However, although the combination group showed complete tumor regression, this difference did not reach statistical significance. But in general, we emphasize that in the case of pre-injection, exosomes have great potential to combat the famous “cold tumor”, ovarian cancer, via targeting omentum and activating anti-tumor immunity, offering a novel avenue for overcoming ovarian cancer.https://doi.org/10.1007/s00262-025-03951-2ExosomesOvarian cancerTumor immune microenvironmentImmunotherapy
spellingShingle Yuanyuan Wang
Changyi Zhang
Huimin Zeng
Liangliang Wang
Zanhong Wang
Zhiqiang Han
Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice
Cancer Immunology, Immunotherapy
Exosomes
Ovarian cancer
Tumor immune microenvironment
Immunotherapy
title Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice
title_full Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice
title_fullStr Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice
title_full_unstemmed Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice
title_short Pre-injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice
title_sort pre injection of exosomes can significantly suppress ovarian cancer growth by activating the immune system in mice
topic Exosomes
Ovarian cancer
Tumor immune microenvironment
Immunotherapy
url https://doi.org/10.1007/s00262-025-03951-2
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