EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human Setting
Cervical cancer is a major cause of cancer death in women worldwide. Targeting human papillomavirus (HPV) viral oncoproteins E6 and E7 is a new strategy for cervical cancer immunotherapy and has been associated with resolution of HPV-induced lesions. How to efficiently induce T cell target killing o...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/11/2/320 |
| _version_ | 1827755288060493824 |
|---|---|
| author | Juan Feng Yongliang Liu Na Zhuang Zixuan Chai Limei Liu Cheng Qian Jiatao Li Juanjuan Shan |
| author_facet | Juan Feng Yongliang Liu Na Zhuang Zixuan Chai Limei Liu Cheng Qian Jiatao Li Juanjuan Shan |
| author_sort | Juan Feng |
| collection | DOAJ |
| description | Cervical cancer is a major cause of cancer death in women worldwide. Targeting human papillomavirus (HPV) viral oncoproteins E6 and E7 is a new strategy for cervical cancer immunotherapy and has been associated with resolution of HPV-induced lesions. How to efficiently induce T cell target killing of HPV infected cervical cancer is of great potential benefit for cervical cancer treatment. Fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for Toll-like receptor 4 (TLR4), and HPVE7 (EDA-E7) has been shown to efficiently induce dendritic cells maturation and trigger specific antitumor CD8+ T cells response in mice. In this study, we constructed EDA-E7 fusion protein of human origin and tested its function in dendritic cell maturation as well as antitumor T cell response. We found that EDA-E7 could be efficiently captured by human PBMC derived dendritic cells (DCs) in vitro and induce DCs maturation. Importantly, this effect could work in synergy with the TLR ligand anti-CD40 agonist, polyinosinic-polycytidylic acid [poly (I:C)], R848, and CpG2216. EDA-E7 matured DCs could activate T cells and trigger an anti-tumor response in vitro. Single cell RNA sequencing and T cell targeted killing assay confirmed the activation of T cells by EDA-E7 matured DCs. Therefore, therapeutic vaccination with EDA-E7 fusion protein maybe effective for human cervical carcinoma treatment. |
| first_indexed | 2024-03-11T08:02:13Z |
| format | Article |
| id | doaj.art-cf91a3a77dde4194b230e7883ff90f7a |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T08:02:13Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-cf91a3a77dde4194b230e7883ff90f7a2023-11-16T23:42:46ZengMDPI AGVaccines2076-393X2023-01-0111232010.3390/vaccines11020320EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human SettingJuan Feng0Yongliang Liu1Na Zhuang2Zixuan Chai3Limei Liu4Cheng Qian5Jiatao Li6Juanjuan Shan7Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, ChinaChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, ChinaChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, ChinaChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, ChinaChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, ChinaChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, ChinaChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, ChinaChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Research Center for Precision Medicine, Chongqing University Cancer Hospital, Chongqing 400030, ChinaCervical cancer is a major cause of cancer death in women worldwide. Targeting human papillomavirus (HPV) viral oncoproteins E6 and E7 is a new strategy for cervical cancer immunotherapy and has been associated with resolution of HPV-induced lesions. How to efficiently induce T cell target killing of HPV infected cervical cancer is of great potential benefit for cervical cancer treatment. Fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for Toll-like receptor 4 (TLR4), and HPVE7 (EDA-E7) has been shown to efficiently induce dendritic cells maturation and trigger specific antitumor CD8+ T cells response in mice. In this study, we constructed EDA-E7 fusion protein of human origin and tested its function in dendritic cell maturation as well as antitumor T cell response. We found that EDA-E7 could be efficiently captured by human PBMC derived dendritic cells (DCs) in vitro and induce DCs maturation. Importantly, this effect could work in synergy with the TLR ligand anti-CD40 agonist, polyinosinic-polycytidylic acid [poly (I:C)], R848, and CpG2216. EDA-E7 matured DCs could activate T cells and trigger an anti-tumor response in vitro. Single cell RNA sequencing and T cell targeted killing assay confirmed the activation of T cells by EDA-E7 matured DCs. Therefore, therapeutic vaccination with EDA-E7 fusion protein maybe effective for human cervical carcinoma treatment.https://www.mdpi.com/2076-393X/11/2/320cervical cancerhuman papillomavirus (HPV)extra domain A (EDA)cancer immunotherapy |
| spellingShingle | Juan Feng Yongliang Liu Na Zhuang Zixuan Chai Limei Liu Cheng Qian Jiatao Li Juanjuan Shan EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human Setting Vaccines cervical cancer human papillomavirus (HPV) extra domain A (EDA) cancer immunotherapy |
| title | EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human Setting |
| title_full | EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human Setting |
| title_fullStr | EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human Setting |
| title_full_unstemmed | EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human Setting |
| title_short | EDA-E7 Activated DCs Induces Cytotoxic T Lymphocyte Immune Responses against HPV Expressing Cervical Cancer in Human Setting |
| title_sort | eda e7 activated dcs induces cytotoxic t lymphocyte immune responses against hpv expressing cervical cancer in human setting |
| topic | cervical cancer human papillomavirus (HPV) extra domain A (EDA) cancer immunotherapy |
| url | https://www.mdpi.com/2076-393X/11/2/320 |
| work_keys_str_mv | AT juanfeng edae7activateddcsinducescytotoxictlymphocyteimmuneresponsesagainsthpvexpressingcervicalcancerinhumansetting AT yongliangliu edae7activateddcsinducescytotoxictlymphocyteimmuneresponsesagainsthpvexpressingcervicalcancerinhumansetting AT nazhuang edae7activateddcsinducescytotoxictlymphocyteimmuneresponsesagainsthpvexpressingcervicalcancerinhumansetting AT zixuanchai edae7activateddcsinducescytotoxictlymphocyteimmuneresponsesagainsthpvexpressingcervicalcancerinhumansetting AT limeiliu edae7activateddcsinducescytotoxictlymphocyteimmuneresponsesagainsthpvexpressingcervicalcancerinhumansetting AT chengqian edae7activateddcsinducescytotoxictlymphocyteimmuneresponsesagainsthpvexpressingcervicalcancerinhumansetting AT jiataoli edae7activateddcsinducescytotoxictlymphocyteimmuneresponsesagainsthpvexpressingcervicalcancerinhumansetting AT juanjuanshan edae7activateddcsinducescytotoxictlymphocyteimmuneresponsesagainsthpvexpressingcervicalcancerinhumansetting |