Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells
Approximately two-thirds of hepatocellular carcinoma (HCC) is considered a “cold tumor” characterized by few tumor-infiltrating T cells and an abundance of immunosuppressive cells. Cilengitide, an integrin αvβ3 inhibitor, has failed in clinical trials as a potential anticancer drug. This failure imp...
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2304963 |
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| author | Mimi Zhou Yali Feng Xiaoli Zhang Jianguo Chen Naijuan Yao Shan Fu Tianzhi Ni Yi Chen Fei Xie Sahasrabda Roy Jinfeng Liu Yuan Yang Yingli He Yingren Zhao Nan Yang |
| author_facet | Mimi Zhou Yali Feng Xiaoli Zhang Jianguo Chen Naijuan Yao Shan Fu Tianzhi Ni Yi Chen Fei Xie Sahasrabda Roy Jinfeng Liu Yuan Yang Yingli He Yingren Zhao Nan Yang |
| author_sort | Mimi Zhou |
| collection | DOAJ |
| description | Approximately two-thirds of hepatocellular carcinoma (HCC) is considered a “cold tumor” characterized by few tumor-infiltrating T cells and an abundance of immunosuppressive cells. Cilengitide, an integrin αvβ3 inhibitor, has failed in clinical trials as a potential anticancer drug. This failure implies that integrin αvβ3 may play an important role in immune cells. However, the expression and potential role of integrin αvβ3 in T cells of HCC patients remain unknown. Here, we established two HCC models and found that cilengitide had a dual effect on the HCC microenvironment by exerting both antitumor effect and immunosuppressive effect on T cells. This may partly explain the failure of cilengitide in clinical trials. In clinical specimens, HCC-infiltrating T cells exhibited deficient expression and activation of integrin β3, which was associated with poor T-cell infiltration into tumors. Additionally, integrin β3 functioned as a positive immunomodulatory molecule to facilitate T-cell infiltration and T helper 1-type immune response in vitro. Furthermore, T cells and platelet-derived microparticles (PMPs) co-culture assay revealed that PMPs adoptively transferred integrin β3 to T cells and positively regulated T cell immune response. This process was mediated by clathrin-dependent endocytosis and macropinocytosis. Our data demonstrate that integrin β3 deficiency on HCC-infiltrating T cells may be involved in shaping the immunosuppressive tumor microenvironment. PMPs transfer integrin β3 to T cells and positively regulate T cell immune response, which may provide a new insight into immune therapy of HCC. |
| format | Article |
| id | doaj-art-065d3b3d163b4f5ab57e81638702dbe7 |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-065d3b3d163b4f5ab57e81638702dbe72025-08-20T02:38:26ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2304963Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cellsMimi Zhou0Yali Feng1Xiaoli Zhang2Jianguo Chen3Naijuan Yao4Shan Fu5Tianzhi Ni6Yi Chen7Fei Xie8Sahasrabda Roy9Jinfeng Liu10Yuan Yang11Yingli He12Yingren Zhao13Nan Yang14Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaSchool of Software Engineering, Sun Yat-Sen University, Zhuhai, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaHealth Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaSchool of International Education, Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaApproximately two-thirds of hepatocellular carcinoma (HCC) is considered a “cold tumor” characterized by few tumor-infiltrating T cells and an abundance of immunosuppressive cells. Cilengitide, an integrin αvβ3 inhibitor, has failed in clinical trials as a potential anticancer drug. This failure implies that integrin αvβ3 may play an important role in immune cells. However, the expression and potential role of integrin αvβ3 in T cells of HCC patients remain unknown. Here, we established two HCC models and found that cilengitide had a dual effect on the HCC microenvironment by exerting both antitumor effect and immunosuppressive effect on T cells. This may partly explain the failure of cilengitide in clinical trials. In clinical specimens, HCC-infiltrating T cells exhibited deficient expression and activation of integrin β3, which was associated with poor T-cell infiltration into tumors. Additionally, integrin β3 functioned as a positive immunomodulatory molecule to facilitate T-cell infiltration and T helper 1-type immune response in vitro. Furthermore, T cells and platelet-derived microparticles (PMPs) co-culture assay revealed that PMPs adoptively transferred integrin β3 to T cells and positively regulated T cell immune response. This process was mediated by clathrin-dependent endocytosis and macropinocytosis. Our data demonstrate that integrin β3 deficiency on HCC-infiltrating T cells may be involved in shaping the immunosuppressive tumor microenvironment. PMPs transfer integrin β3 to T cells and positively regulate T cell immune response, which may provide a new insight into immune therapy of HCC.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2304963Hepatocellular carcinomaintegrin αvβ3platelet-derived microparticlestumor-infiltrating lymphocytes |
| spellingShingle | Mimi Zhou Yali Feng Xiaoli Zhang Jianguo Chen Naijuan Yao Shan Fu Tianzhi Ni Yi Chen Fei Xie Sahasrabda Roy Jinfeng Liu Yuan Yang Yingli He Yingren Zhao Nan Yang Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells OncoImmunology Hepatocellular carcinoma integrin αvβ3 platelet-derived microparticles tumor-infiltrating lymphocytes |
| title | Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells |
| title_full | Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells |
| title_fullStr | Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells |
| title_full_unstemmed | Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells |
| title_short | Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells |
| title_sort | platelet derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor infiltrating t cells |
| topic | Hepatocellular carcinoma integrin αvβ3 platelet-derived microparticles tumor-infiltrating lymphocytes |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2304963 |
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