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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Main Authors: Yulong Zhou, Xiyang Tang, Weiguang Du, Chen Shu, Xiaolong Yan, Nan Ma, Jinbo Zhao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
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.
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institution DOAJ
issn 1664-3224
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publisher Frontiers Media S.A.
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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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