{"title":"HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer.","authors":"Christiane Gruetzmacher, Bruna Sousa Pessoa, Flora Ladeira Craveiro, Marilena Nakaguma, Ericka Barbosa Trarbach, Rafael Loch Batista","doi":"10.1530/EO-24-0034","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"5 1","pages":"e240034"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007912/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine oncology (Bristol, England)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1530/EO-24-0034","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract
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.
目的：人内源性逆转录病毒- h长末端重复相关2 （HHLA2）是B7家族的一员，在人类癌症中广泛表达，并正在成为治疗开发的有希望的免疫检查点靶点。本研究旨在巩固HHLA2在内分泌相关癌症中表达的现有数据，并评估其作为预后生物标志物的潜力。方法：使用PubMed、Web of Science和Embase数据库检索截至2024年12月发表的英文原始研究。搜索策略将MeSH术语与“HHLA2”、“B7-H7”、“B7y”、“B7-H5”和“癌症”相关的关键词结合起来，特别关注与内分泌相关的癌症。结果：共纳入117项研究，其中12项符合纳入标准。7项胰腺癌研究显示HHLA2表达模式不同，高表达水平与更好的预后和提高的总生存率相关。在卵巢癌中，一项研究表明，HHLA2在肿瘤细胞中的高表达可以预测生存率的提高。相比之下，另一项研究将HHLA2与淋巴结转移和较差的总生存率联系起来，仅在基质细胞中观察到高表达。另一方面，甲状腺癌和神经内分泌肿瘤的研究强调了HHLA2在疾病进展中的重要意义，提示其预后不良并与转移有关。结论：HHLA2在内分泌相关肿瘤中具有免疫抑制和肿瘤抑制双重作用，其表达可能受肿瘤微环境的影响。这凸显了它作为免疫检查点生物标志物和治疗靶点的前景。本综述的总体数据为未来hhla2相关肿瘤学的研究工作提供了见解。
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