Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancer
Abstract Although the programmed cell death protein 1 (PD-1) blockade has been authorized for the treatment of recurrent and metastatic cervical cancer (CC) patients, a significant proportion of CC patients show low objective response rates (ORR) to immune checkpoint blockades (ICBs). Therefore, ide...
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2025-06-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03500-0 |
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| author | Lili Jiang Tong Wu Xinyu Qu Shuqi Li Qi’an Jiang Tingting Ren Jiali Liang Yan Ding Keqin Hua Zhongmin Tang Junjun Qiu |
| author_facet | Lili Jiang Tong Wu Xinyu Qu Shuqi Li Qi’an Jiang Tingting Ren Jiali Liang Yan Ding Keqin Hua Zhongmin Tang Junjun Qiu |
| author_sort | Lili Jiang |
| collection | DOAJ |
| description | Abstract Although the programmed cell death protein 1 (PD-1) blockade has been authorized for the treatment of recurrent and metastatic cervical cancer (CC) patients, a significant proportion of CC patients show low objective response rates (ORR) to immune checkpoint blockades (ICBs). Therefore, identifying novel combination treatment strategies to enhance ICBs therapeutic efficacy for CC patients is urgently needed. Here, we discovered that CD39 was highly expressed in exhausted CD8 + T cells from 10 CC patients in our center via single-cell RNA sequencing (scRNA-seq). Furthermore, we validated that CC patients with CD39 highly expressed in CD8 + T cells associated with poor prognosis and immunoevasive subtype of CC both in cohort from our center and the Cancer Genome Atlas (TCGA) database. Moreover, it was also confirmed that CD39-inhibiting not only enhanced the cytotoxicity of CD8 + tumor-infiltrating lymphocytes (TILs) but also promoted the infiltration of B cells through increasing CXCL13 secretion both in vitro experiments and subcutaneous tumor models, thereby amplifying anti-tumor immunity of PD-1 blockade. What was more, we have developed a liposome containing POM-1, which effectively enhanced the anti-tumor effect of POM-1. Our findings provide compelling evidence that targeting CD39 represents a promising “two birds with one stone” strategy for cervical cancer treatment. |
| format | Article |
| id | doaj-art-4b3ecb4e7ef04bb39dfc24dd27f62b58 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-4b3ecb4e7ef04bb39dfc24dd27f62b582025-08-20T02:30:59ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123112110.1186/s12951-025-03500-0Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancerLili Jiang0Tong Wu1Xinyu Qu2Shuqi Li3Qi’an Jiang4Tingting Ren5Jiali Liang6Yan Ding7Keqin Hua8Zhongmin Tang9Junjun Qiu10Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Cardiology, School of Medicine, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityAbstract Although the programmed cell death protein 1 (PD-1) blockade has been authorized for the treatment of recurrent and metastatic cervical cancer (CC) patients, a significant proportion of CC patients show low objective response rates (ORR) to immune checkpoint blockades (ICBs). Therefore, identifying novel combination treatment strategies to enhance ICBs therapeutic efficacy for CC patients is urgently needed. Here, we discovered that CD39 was highly expressed in exhausted CD8 + T cells from 10 CC patients in our center via single-cell RNA sequencing (scRNA-seq). Furthermore, we validated that CC patients with CD39 highly expressed in CD8 + T cells associated with poor prognosis and immunoevasive subtype of CC both in cohort from our center and the Cancer Genome Atlas (TCGA) database. Moreover, it was also confirmed that CD39-inhibiting not only enhanced the cytotoxicity of CD8 + tumor-infiltrating lymphocytes (TILs) but also promoted the infiltration of B cells through increasing CXCL13 secretion both in vitro experiments and subcutaneous tumor models, thereby amplifying anti-tumor immunity of PD-1 blockade. What was more, we have developed a liposome containing POM-1, which effectively enhanced the anti-tumor effect of POM-1. Our findings provide compelling evidence that targeting CD39 represents a promising “two birds with one stone” strategy for cervical cancer treatment.https://doi.org/10.1186/s12951-025-03500-0Cervical cancer (CC)Tumor microenvironmentImmune checkpoint blockage (ICB)αCD39B cellsExhausted T cells |
| spellingShingle | Lili Jiang Tong Wu Xinyu Qu Shuqi Li Qi’an Jiang Tingting Ren Jiali Liang Yan Ding Keqin Hua Zhongmin Tang Junjun Qiu Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancer Journal of Nanobiotechnology Cervical cancer (CC) Tumor microenvironment Immune checkpoint blockage (ICB) αCD39 B cells Exhausted T cells |
| title | Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancer |
| title_full | Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancer |
| title_fullStr | Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancer |
| title_full_unstemmed | Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancer |
| title_short | Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancer |
| title_sort | targeting cd39 boosts pd 1 blockade antitumor therapeutic efficacy via strengthening cd8 tils function and recruiting b cells in cervical cancer |
| topic | Cervical cancer (CC) Tumor microenvironment Immune checkpoint blockage (ICB) αCD39 B cells Exhausted T cells |
| url | https://doi.org/10.1186/s12951-025-03500-0 |
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