Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy
CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory recep...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-06-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417302207 |
| _version_ | 1817986620690792448 |
|---|---|
| author | Jie-Jie Geng Juan Tang Xiang-min Yang Ruo Chen Yang Zhang Kui Zhang Jin-Lin Miao Zhi-Nan Chen Ping Zhu |
| author_facet | Jie-Jie Geng Juan Tang Xiang-min Yang Ruo Chen Yang Zhang Kui Zhang Jin-Lin Miao Zhi-Nan Chen Ping Zhu |
| author_sort | Jie-Jie Geng |
| collection | DOAJ |
| description | CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative) and fully committed DP (double positive) cells into innate NK-like lineages. Mechanistically, CD147 deficiency results in impaired Wnt signaling and expression of BCL11b, a master transcription factor in determining T cell identity. In addition, functional blocking of CD147 by antibody phenocopies genetic deletion to enrich NK-like cells in the periphery. Furthermore, using a melanoma model and orthotopic liver cancer transplants, we showed that the augmentation of NK-like cells strongly associates with resistance against tumor growth upon CD147 suppression. Therefore, besides its original function in tumorigenesis, CD147 is also an effective surface target for immune modulation in tumor therapy. |
| first_indexed | 2024-04-14T00:11:36Z |
| format | Article |
| id | doaj.art-8c427bdca82243e8b4d390057b95f907 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-14T00:11:36Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-8c427bdca82243e8b4d390057b95f9072022-12-22T02:23:19ZengElsevierEBioMedicine2352-39642017-06-0120C9810810.1016/j.ebiom.2017.05.022Targeting CD147 for T to NK Lineage Reprogramming and Tumor TherapyJie-Jie Geng0Juan Tang1Xiang-min Yang2Ruo Chen3Yang Zhang4Kui Zhang5Jin-Lin Miao6Zhi-Nan Chen7Ping Zhu8Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaDepartment of Cell Biology, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaDepartment of Cell Biology, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaDepartment of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaDepartment of Cell Biology, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaDepartment of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaDepartment of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaDepartment of Cell Biology, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaDepartment of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shan'xi 710032, PR ChinaCD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative) and fully committed DP (double positive) cells into innate NK-like lineages. Mechanistically, CD147 deficiency results in impaired Wnt signaling and expression of BCL11b, a master transcription factor in determining T cell identity. In addition, functional blocking of CD147 by antibody phenocopies genetic deletion to enrich NK-like cells in the periphery. Furthermore, using a melanoma model and orthotopic liver cancer transplants, we showed that the augmentation of NK-like cells strongly associates with resistance against tumor growth upon CD147 suppression. Therefore, besides its original function in tumorigenesis, CD147 is also an effective surface target for immune modulation in tumor therapy.http://www.sciencedirect.com/science/article/pii/S2352396417302207BCL11bCancer immune-therapyCD147Trans-differentiationThymocyte development |
| spellingShingle | Jie-Jie Geng Juan Tang Xiang-min Yang Ruo Chen Yang Zhang Kui Zhang Jin-Lin Miao Zhi-Nan Chen Ping Zhu Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy EBioMedicine BCL11b Cancer immune-therapy CD147 Trans-differentiation Thymocyte development |
| title | Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy |
| title_full | Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy |
| title_fullStr | Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy |
| title_full_unstemmed | Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy |
| title_short | Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy |
| title_sort | targeting cd147 for t to nk lineage reprogramming and tumor therapy |
| topic | BCL11b Cancer immune-therapy CD147 Trans-differentiation Thymocyte development |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417302207 |
| work_keys_str_mv | AT jiejiegeng targetingcd147forttonklineagereprogrammingandtumortherapy AT juantang targetingcd147forttonklineagereprogrammingandtumortherapy AT xiangminyang targetingcd147forttonklineagereprogrammingandtumortherapy AT ruochen targetingcd147forttonklineagereprogrammingandtumortherapy AT yangzhang targetingcd147forttonklineagereprogrammingandtumortherapy AT kuizhang targetingcd147forttonklineagereprogrammingandtumortherapy AT jinlinmiao targetingcd147forttonklineagereprogrammingandtumortherapy AT zhinanchen targetingcd147forttonklineagereprogrammingandtumortherapy AT pingzhu targetingcd147forttonklineagereprogrammingandtumortherapy |