HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer

Purpose: Human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), a member of the B7 family, is widely expressed across human cancers and is emerging as a promising immune checkpoint target for therapeutic development. This study aims to consolidate existing data on HHLA2 expression...

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Main Authors: Christiane Gruetzmacher, Bruna Sousa Pessoa, Flora Ladeira Craveiro, Marilena Nakaguma, Ericka Barbosa Trarbach, Rafael Loch Batista
Format: Article
Language:English
Published: Bioscientifica 2025-04-01
Series:Endocrine Oncology
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Online Access:https://eo.bioscientifica.com/view/journals/eo/5/1/EO-24-0034.xml
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author Christiane Gruetzmacher
Bruna Sousa Pessoa
Flora Ladeira Craveiro
Marilena Nakaguma
Ericka Barbosa Trarbach
Rafael Loch Batista
author_facet Christiane Gruetzmacher
Bruna Sousa Pessoa
Flora Ladeira Craveiro
Marilena Nakaguma
Ericka Barbosa Trarbach
Rafael Loch Batista
author_sort Christiane Gruetzmacher
collection DOAJ
description Purpose: Human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), a member of the B7 family, is widely expressed across human cancers and is emerging as a promising immune checkpoint target for therapeutic development. This study aims to consolidate existing data on HHLA2 expression in endocrine-related cancers and evaluate its potential as a prognostic biomarker. Methods: Original studies published in English up to December 2024 were searched using PubMed, Web of Science and Embase databases. Search strategies combined MeSH terms and keywords related to ‘HHLA2’, ‘B7-H7’, ‘B7y’, ‘B7-H5’ and ‘cancer’, with a specific focus on endocrine-related cancers. Results: From a total of 117 studies reviewed, twelve met the inclusion criteria. Seven studies on pancreatic cancer indicated varied HHLA2 expression patterns, with high expression levels associated with better prognosis and improved overall survival. In ovarian cancer, one study suggested that high HHLA2 expression in tumor cells could predict improved survival. In contrast, another study linked HHLA2 to lymph node metastasis and poor overall survival, observing high expression only in stromal cells. On the other hand, studies on thyroid cancer and neuroendocrine tumors highlighted HHLA2’s significance in disease progression, indicating poor prognosis and its association with metastasis. Conclusion: HHLA2 plays dual roles, exhibiting both immunosuppressive and tumor-suppressive functions in endocrine-related tumors, with its expression possibly influenced by the tumor microenvironment. This highlights its promise as an immune checkpoint biomarker and therapeutic target. The collective data from this review provide insights for future research endeavors in HHLA2-associated oncology.
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spelling doaj-art-edccccc54d9c4bac931d499fb3d878402025-08-20T03:18:09ZengBioscientificaEndocrine Oncology2634-47932025-04-015110.1530/EO-24-00341HHLA2: a potential biomarker and therapeutic target in endocrine-related cancerChristiane Gruetzmacher0Bruna Sousa Pessoa1Flora Ladeira Craveiro2Marilena Nakaguma3Ericka Barbosa Trarbach4Rafael Loch Batista5Neuroendocrinology Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, BrazilNeuroendocrinology Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, BrazilNeuroendocrinology Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, BrazilNeuroendocrinology Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, BrazilNeuroendocrinology Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, BrazilNeuroendocrinology Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, BrazilPurpose: Human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), a member of the B7 family, is widely expressed across human cancers and is emerging as a promising immune checkpoint target for therapeutic development. This study aims to consolidate existing data on HHLA2 expression in endocrine-related cancers and evaluate its potential as a prognostic biomarker. Methods: Original studies published in English up to December 2024 were searched using PubMed, Web of Science and Embase databases. Search strategies combined MeSH terms and keywords related to ‘HHLA2’, ‘B7-H7’, ‘B7y’, ‘B7-H5’ and ‘cancer’, with a specific focus on endocrine-related cancers. Results: From a total of 117 studies reviewed, twelve met the inclusion criteria. Seven studies on pancreatic cancer indicated varied HHLA2 expression patterns, with high expression levels associated with better prognosis and improved overall survival. In ovarian cancer, one study suggested that high HHLA2 expression in tumor cells could predict improved survival. In contrast, another study linked HHLA2 to lymph node metastasis and poor overall survival, observing high expression only in stromal cells. On the other hand, studies on thyroid cancer and neuroendocrine tumors highlighted HHLA2’s significance in disease progression, indicating poor prognosis and its association with metastasis. Conclusion: HHLA2 plays dual roles, exhibiting both immunosuppressive and tumor-suppressive functions in endocrine-related tumors, with its expression possibly influenced by the tumor microenvironment. This highlights its promise as an immune checkpoint biomarker and therapeutic target. The collective data from this review provide insights for future research endeavors in HHLA2-associated oncology.https://eo.bioscientifica.com/view/journals/eo/5/1/EO-24-0034.xmlhhla2biomarkertherapeutic targetendocrine-related cancerimmune checkpointcancer immunotherapy
spellingShingle Christiane Gruetzmacher
Bruna Sousa Pessoa
Flora Ladeira Craveiro
Marilena Nakaguma
Ericka Barbosa Trarbach
Rafael Loch Batista
HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer
Endocrine Oncology
hhla2
biomarker
therapeutic target
endocrine-related cancer
immune checkpoint
cancer immunotherapy
title HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer
title_full HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer
title_fullStr HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer
title_full_unstemmed HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer
title_short HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer
title_sort hhla2 a potential biomarker and therapeutic target in endocrine related cancer
topic hhla2
biomarker
therapeutic target
endocrine-related cancer
immune checkpoint
cancer immunotherapy
url https://eo.bioscientifica.com/view/journals/eo/5/1/EO-24-0034.xml
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