CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer
Background: Ovarian cancer, ranking fifth in cancer mortality, presents a significant therapeutic challenge. The immunomodulatory functions of CD38in epithelial ovarian cancer (EOC) and its influence on the tumor microenvironment (TME) remain poorly understood. Methods: Public datasets, RT-qPCR and...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325001457 |
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| author | Wei Wang Xiangnan Liu Shengjie Xu Enci Dai Yingying Li Yinping Liu Liyun Shan Yanli Li |
| author_facet | Wei Wang Xiangnan Liu Shengjie Xu Enci Dai Yingying Li Yinping Liu Liyun Shan Yanli Li |
| author_sort | Wei Wang |
| collection | DOAJ |
| description | Background: Ovarian cancer, ranking fifth in cancer mortality, presents a significant therapeutic challenge. The immunomodulatory functions of CD38in epithelial ovarian cancer (EOC) and its influence on the tumor microenvironment (TME) remain poorly understood. Methods: Public datasets, RT-qPCR and immunohistochemistry (IHC) were used to analyze CD38 expression and clinicopathological features in EOC. Gene manipulation techniques were employed to elucidate its functions, while integrated IHC and bioinformatics were conducted to assess its involvement in immune/stromal infiltration. Immune-related functions of CD38 were explored using GO, KEGG analysis and TIP database. TIDE algorithm was employed to predict the correlation between CD38 and immune checkpoint blocking responsiveness. CD38 inhibitor efficacy was evaluated in an EOC mouse model, with flow cytometry monitoring cellular changes. The involvement of CD38 in the PI3K-AKT and IL-6 signaling pathways was evaluated using RT-qPCR, western blot, and publicly datasets. Results: CD38 is significantly upregulated in EOC, influencing the cell proliferation and metastasis. It regulates the PI3K-AKT and IL-6 signaling pathways, thereby increasing tumor malignancy. CD38 is also upregulated in immune and stromal cells, affecting TME remodeling by facilitating immune cell and CAF infiltration, impeding T cell recognition of tumor cells, and enhancing CAF-tumor cell communication. Additionally, CD38 correlates with multiple immune checkpoint molecules. Notably, CD38 inhibitor therapy inhibited effectively EOC progression and modulates immune responses. Conclusion: Elevated CD38 expression is associated with EOC progression, TME remodeling, and immune response modulation. Thus, CD38 could be a promising target for ovarian cancer immunotherapy. |
| format | Article |
| id | doaj-art-39225dc9d67f4e258a3af004c607f8f3 |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-39225dc9d67f4e258a3af004c607f8f32025-08-20T02:26:10ZengElsevierTranslational Oncology1936-52332025-07-015710241410.1016/j.tranon.2025.102414CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancerWei Wang0Xiangnan Liu1Shengjie Xu2Enci Dai3Yingying Li4Yinping Liu5Liyun Shan6Yanli Li7Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of ChinaDepartment of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of ChinaDepartment of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of ChinaDepartment of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of ChinaDepartment of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of ChinaDepartment of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of ChinaCorresponding authors at: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Post code:201600,650 Xingsongjiang Road, Shanghai, China.; Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of ChinaCorresponding authors at: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Post code:201600,650 Xingsongjiang Road, Shanghai, China.; Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of ChinaBackground: Ovarian cancer, ranking fifth in cancer mortality, presents a significant therapeutic challenge. The immunomodulatory functions of CD38in epithelial ovarian cancer (EOC) and its influence on the tumor microenvironment (TME) remain poorly understood. Methods: Public datasets, RT-qPCR and immunohistochemistry (IHC) were used to analyze CD38 expression and clinicopathological features in EOC. Gene manipulation techniques were employed to elucidate its functions, while integrated IHC and bioinformatics were conducted to assess its involvement in immune/stromal infiltration. Immune-related functions of CD38 were explored using GO, KEGG analysis and TIP database. TIDE algorithm was employed to predict the correlation between CD38 and immune checkpoint blocking responsiveness. CD38 inhibitor efficacy was evaluated in an EOC mouse model, with flow cytometry monitoring cellular changes. The involvement of CD38 in the PI3K-AKT and IL-6 signaling pathways was evaluated using RT-qPCR, western blot, and publicly datasets. Results: CD38 is significantly upregulated in EOC, influencing the cell proliferation and metastasis. It regulates the PI3K-AKT and IL-6 signaling pathways, thereby increasing tumor malignancy. CD38 is also upregulated in immune and stromal cells, affecting TME remodeling by facilitating immune cell and CAF infiltration, impeding T cell recognition of tumor cells, and enhancing CAF-tumor cell communication. Additionally, CD38 correlates with multiple immune checkpoint molecules. Notably, CD38 inhibitor therapy inhibited effectively EOC progression and modulates immune responses. Conclusion: Elevated CD38 expression is associated with EOC progression, TME remodeling, and immune response modulation. Thus, CD38 could be a promising target for ovarian cancer immunotherapy.http://www.sciencedirect.com/science/article/pii/S1936523325001457CD38Epithelial ovarian cancerTumor microenvironmentCD38 inhibitoImmunotherapy |
| spellingShingle | Wei Wang Xiangnan Liu Shengjie Xu Enci Dai Yingying Li Yinping Liu Liyun Shan Yanli Li CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer Translational Oncology CD38 Epithelial ovarian cancer Tumor microenvironment CD38 inhibito Immunotherapy |
| title | CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer |
| title_full | CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer |
| title_fullStr | CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer |
| title_full_unstemmed | CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer |
| title_short | CD38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer |
| title_sort | cd38 contributes to tumor progression and tumor microenvironment reshaping in epithelial ovarian cancer |
| topic | CD38 Epithelial ovarian cancer Tumor microenvironment CD38 inhibito Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325001457 |
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