Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors
Therapies targeting immune checkpoints like programmed death receptor-1 and programmed death ligand-1 have demonstrated remarkable effectiveness in combating cancer. However, a subset of patients fails to respond to these therapies, underscoring the complexity of tumor immune evasion mechanisms. Exp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612234/full |
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| author | Yulong Zhou Xiyang Tang Weiguang Du Chen Shu Chen Shu Xiaolong Yan Nan Ma Jinbo Zhao |
| author_facet | Yulong Zhou Xiyang Tang Weiguang Du Chen Shu Chen Shu Xiaolong Yan Nan Ma Jinbo Zhao |
| author_sort | Yulong Zhou |
| collection | DOAJ |
| description | Therapies targeting immune checkpoints like programmed death receptor-1 and programmed death ligand-1 have demonstrated remarkable effectiveness in combating cancer. However, a subset of patients fails to respond to these therapies, underscoring the complexity of tumor immune evasion mechanisms. Exploring innovative immune regulatory targets represents a crucial research priority in this field. Signal regulatory protein α (SIRPα) is an immunosuppressive receptor expressed on myeloid cells that inhibits innate immunity through its interaction with the ligand integrin-associated protein (CD47). Blocking the SIRPα–CD47 axis can enhance myeloid cell-mediated anti-tumor responses and stimulate adaptive immunity, thereby synergizing with therapeutic antibodies and T-cell checkpoint inhibitors. Additionally, tumor-intrinsic SIRPα may facilitate tumor growth and immune evasion. This paper aims to elucidate the mechanisms of SIRPα activity in various cell types, review the advancements in SIRPα-targeted tumor therapies, and highlight the potential research value of tumor-expressed endogenous SIRPα. |
| format | Article |
| id | doaj-art-45dd792cecf94ee4985a6e59ff461d4e |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-45dd792cecf94ee4985a6e59ff461d4e2025-08-20T03:20:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16122341612234Deciphering the role of signal regulatory protein α in immunotherapy for solid tumorsYulong Zhou0Xiyang Tang1Weiguang Du2Chen Shu3Chen Shu4Xiaolong Yan5Nan Ma6Jinbo Zhao7Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Cardiothoracic Surgery, The 902nd Hospital of the Chinese People’s Liberation Army Joint Logistic Support Force, Bengbu, Anhui, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Ophthalmology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, ChinaTherapies targeting immune checkpoints like programmed death receptor-1 and programmed death ligand-1 have demonstrated remarkable effectiveness in combating cancer. However, a subset of patients fails to respond to these therapies, underscoring the complexity of tumor immune evasion mechanisms. Exploring innovative immune regulatory targets represents a crucial research priority in this field. Signal regulatory protein α (SIRPα) is an immunosuppressive receptor expressed on myeloid cells that inhibits innate immunity through its interaction with the ligand integrin-associated protein (CD47). Blocking the SIRPα–CD47 axis can enhance myeloid cell-mediated anti-tumor responses and stimulate adaptive immunity, thereby synergizing with therapeutic antibodies and T-cell checkpoint inhibitors. Additionally, tumor-intrinsic SIRPα may facilitate tumor growth and immune evasion. This paper aims to elucidate the mechanisms of SIRPα activity in various cell types, review the advancements in SIRPα-targeted tumor therapies, and highlight the potential research value of tumor-expressed endogenous SIRPα.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612234/fullCD47immunotherapyimmune checkpoint inhibitorSIRPαsolid tumor |
| spellingShingle | Yulong Zhou Xiyang Tang Weiguang Du Chen Shu Chen Shu Xiaolong Yan Nan Ma Jinbo Zhao Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors Frontiers in Immunology CD47 immunotherapy immune checkpoint inhibitor SIRPα solid tumor |
| title | Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors |
| title_full | Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors |
| title_fullStr | Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors |
| title_full_unstemmed | Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors |
| title_short | Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors |
| title_sort | deciphering the role of signal regulatory protein α in immunotherapy for solid tumors |
| topic | CD47 immunotherapy immune checkpoint inhibitor SIRPα solid tumor |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612234/full |
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