TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells
This study is sought to determine the physiological mechanisms by which exosomes-encapsulated TIM-3 derived from melanoma cells might mediate CD4+ T cell immune function and macrophage M2 polarization in melanoma. Initially, exosomes were isolated from the human skin-derived melanoma cell line MV3fo...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523321003259 |
| _version_ | 1818329816703696896 |
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| author | Xinghui Li Yu Liu Li Yang Yannan Jiang Qihong Qian |
| author_facet | Xinghui Li Yu Liu Li Yang Yannan Jiang Qihong Qian |
| author_sort | Xinghui Li |
| collection | DOAJ |
| description | This study is sought to determine the physiological mechanisms by which exosomes-encapsulated TIM-3 derived from melanoma cells might mediate CD4+ T cell immune function and macrophage M2 polarization in melanoma. Initially, exosomes were isolated from the human skin-derived melanoma cell line MV3for analysis of TIM-3 expression pattern. Next, the exosomes sourced from MV3 cells manipulated with sh-TIM-3 were co-incubated with CD4+ T cells to detect CD4+ T cell proliferation and MV3 cell migration and invasion, to observe the macrophage M2 polarization, and to determine levels of several EMT-related factors. Finally, melanoma nude mouse models were established to study the in vivo modulatory effects of TIM-3 from MV3 cells-derived exosomes. MV3 cells-derived exosomes inhibited CD4+ T cell immune function and promoted macrophage M2 polarization in melanoma. Our results revealed the abundance of TIM-3 in MV3 cells-derived exosomes. Of importance, silencing of TIM-3 shuttled by MV3 cells-derived exosomes improved CD4+ T cell immune function and inhibited macrophage M2 polarization to attenuate the growth and metastasis of melanoma cells. Collectively, MV3 cells-derived exosomes-loaded TIM-3 suppressed CD4+ T cell immune function and induced macrophage M2 polarization to improve occurrence and development of melanoma, therefore providing us with a potential therapeutic target for effectively combating melanoma. |
| first_indexed | 2024-12-13T12:54:04Z |
| format | Article |
| id | doaj.art-53071c19b6bd48b18c991f8e5bdd1fbe |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-13T12:54:04Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-53071c19b6bd48b18c991f8e5bdd1fbe2022-12-21T23:45:15ZengElsevierTranslational Oncology1936-52332022-04-0118101334TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cellsXinghui Li0Yu Liu1Li Yang2Yannan Jiang3Qihong Qian4Department of Dermatology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P R China; Department of Dermatology, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School/The First People's Hospital of Yancheng, Yancheng 224001, P R ChinaDepartment of Dermatology, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School/The First People's Hospital of Yancheng, Yancheng 224001, P R ChinaDepartment of Dermatology, Shaanxi Provincial People's Hospital, Xi'an 710068, P R ChinaDepartment of Dermatology, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School/The First People's Hospital of Yancheng, Yancheng 224001, P R ChinaDepartment of Dermatology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P R China; Corresponding author at: Department of Dermatology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, P R China.This study is sought to determine the physiological mechanisms by which exosomes-encapsulated TIM-3 derived from melanoma cells might mediate CD4+ T cell immune function and macrophage M2 polarization in melanoma. Initially, exosomes were isolated from the human skin-derived melanoma cell line MV3for analysis of TIM-3 expression pattern. Next, the exosomes sourced from MV3 cells manipulated with sh-TIM-3 were co-incubated with CD4+ T cells to detect CD4+ T cell proliferation and MV3 cell migration and invasion, to observe the macrophage M2 polarization, and to determine levels of several EMT-related factors. Finally, melanoma nude mouse models were established to study the in vivo modulatory effects of TIM-3 from MV3 cells-derived exosomes. MV3 cells-derived exosomes inhibited CD4+ T cell immune function and promoted macrophage M2 polarization in melanoma. Our results revealed the abundance of TIM-3 in MV3 cells-derived exosomes. Of importance, silencing of TIM-3 shuttled by MV3 cells-derived exosomes improved CD4+ T cell immune function and inhibited macrophage M2 polarization to attenuate the growth and metastasis of melanoma cells. Collectively, MV3 cells-derived exosomes-loaded TIM-3 suppressed CD4+ T cell immune function and induced macrophage M2 polarization to improve occurrence and development of melanoma, therefore providing us with a potential therapeutic target for effectively combating melanoma.http://www.sciencedirect.com/science/article/pii/S1936523321003259Mv3 cellsExosomesTim-3MelanomaCd4+ t cell immune functionMacrophage m2 polarization |
| spellingShingle | Xinghui Li Yu Liu Li Yang Yannan Jiang Qihong Qian TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells Translational Oncology Mv3 cells Exosomes Tim-3 Melanoma Cd4+ t cell immune function Macrophage m2 polarization |
| title | TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells |
| title_full | TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells |
| title_fullStr | TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells |
| title_full_unstemmed | TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells |
| title_short | TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells |
| title_sort | tim 3 shuttled by mv3 cells secreted exosomes inhibits cd4 t cell immune function and induces macrophage m2 polarization to promote the growth and metastasis of melanoma cells |
| topic | Mv3 cells Exosomes Tim-3 Melanoma Cd4+ t cell immune function Macrophage m2 polarization |
| url | http://www.sciencedirect.com/science/article/pii/S1936523321003259 |
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