B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature

B7-H3 (CD276), a member of the B7 immune checkpoint family, plays a critical role in modulating immune responses and has emerged as a promising target in cancer therapy. It is highly expressed in various malignancies, where it promotes tumor evasion from T cell surveillance and contributes to cancer...

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Main Authors: Sylwia Mielcarska, Anna Kot, Agnieszka Kula, Miriam Dawidowicz, Piotr Sobków, Daria Kłaczka, Dariusz Waniczek, Elżbieta Świętochowska
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/7/530
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author Sylwia Mielcarska
Anna Kot
Agnieszka Kula
Miriam Dawidowicz
Piotr Sobków
Daria Kłaczka
Dariusz Waniczek
Elżbieta Świętochowska
author_facet Sylwia Mielcarska
Anna Kot
Agnieszka Kula
Miriam Dawidowicz
Piotr Sobków
Daria Kłaczka
Dariusz Waniczek
Elżbieta Świętochowska
author_sort Sylwia Mielcarska
collection DOAJ
description B7-H3 (CD276), a member of the B7 immune checkpoint family, plays a critical role in modulating immune responses and has emerged as a promising target in cancer therapy. It is highly expressed in various malignancies, where it promotes tumor evasion from T cell surveillance and contributes to cancer progression, metastasis, and therapeutic resistance, showing a correlation with the poor prognosis of patients. Although its receptors were not fully identified, B7-H3 signaling involves key intracellular pathways, including JAK/STAT, NF-κB, PI3K/Akt, and MAPK, driving processes crucial for supporting tumor growth such as cell proliferation, invasion, and apoptosis inhibition. Beyond immune modulation, B7-H3 influences cancer cell metabolism, angiogenesis, and epithelial-to-mesenchymal transition, further exacerbating tumor aggressiveness. The development of B7-H3-targeting therapies, including monoclonal antibodies, antibody–drug conjugates, and CAR-T cells, offers promising avenues for treatment. This review provides an up-to-date summary of the B7H3 mechanisms of action, putative receptors, and ongoing clinical trials evaluating therapies targeting B7H3, focusing on the molecule’s role in gastrointestinal tumors.
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spelling doaj-art-7cd091d502094a30baf9ccd2ad13fc872025-08-20T03:08:46ZengMDPI AGCells2073-44092025-04-0114753010.3390/cells14070530B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the LiteratureSylwia Mielcarska0Anna Kot1Agnieszka Kula2Miriam Dawidowicz3Piotr Sobków4Daria Kłaczka5Dariusz Waniczek6Elżbieta Świętochowska7Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-800 Zabrze, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-800 Zabrze, PolandDepartment of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-514 Katowice, PolandDepartment of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-514 Katowice, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-800 Zabrze, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-800 Zabrze, PolandDepartment of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-514 Katowice, PolandDepartment of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-800 Zabrze, PolandB7-H3 (CD276), a member of the B7 immune checkpoint family, plays a critical role in modulating immune responses and has emerged as a promising target in cancer therapy. It is highly expressed in various malignancies, where it promotes tumor evasion from T cell surveillance and contributes to cancer progression, metastasis, and therapeutic resistance, showing a correlation with the poor prognosis of patients. Although its receptors were not fully identified, B7-H3 signaling involves key intracellular pathways, including JAK/STAT, NF-κB, PI3K/Akt, and MAPK, driving processes crucial for supporting tumor growth such as cell proliferation, invasion, and apoptosis inhibition. Beyond immune modulation, B7-H3 influences cancer cell metabolism, angiogenesis, and epithelial-to-mesenchymal transition, further exacerbating tumor aggressiveness. The development of B7-H3-targeting therapies, including monoclonal antibodies, antibody–drug conjugates, and CAR-T cells, offers promising avenues for treatment. This review provides an up-to-date summary of the B7H3 mechanisms of action, putative receptors, and ongoing clinical trials evaluating therapies targeting B7H3, focusing on the molecule’s role in gastrointestinal tumors.https://www.mdpi.com/2073-4409/14/7/530B7H3 (CD276)immune checkpointgastrointestinal cancersimmunotherapy
spellingShingle Sylwia Mielcarska
Anna Kot
Agnieszka Kula
Miriam Dawidowicz
Piotr Sobków
Daria Kłaczka
Dariusz Waniczek
Elżbieta Świętochowska
B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature
Cells
B7H3 (CD276)
immune checkpoint
gastrointestinal cancers
immunotherapy
title B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature
title_full B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature
title_fullStr B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature
title_full_unstemmed B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature
title_short B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature
title_sort b7h3 in gastrointestinal tumors role in immune modulation and cancer progression a review of the literature
topic B7H3 (CD276)
immune checkpoint
gastrointestinal cancers
immunotherapy
url https://www.mdpi.com/2073-4409/14/7/530
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