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Immunol. 15:1495283 .  \ndoi: 10.3389/fimmu.2024.1495283  \nCOPYRIGHT  \n© 2024 Babiˇc, Jovˇcevska and Zottel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nB7-H3 in glioblastoma and beyond: significance and therapeutic strategies  \nDavor Babiˇc, Ivana Jovˇcevska † and Alja Zottel*†  \nCentre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia  \nCancer has emerged as the second most prevalent disease and the leading cause of death, claiming the lives of 10 million individuals each year. The predominant varieties of cancer encompass breast, lung, colon, rectal, and prostate cancers. Among the more aggressive malignancies is glioblastoma, categorized as WHO stage 4 brain cancer. Following diagnosis, the typical life expectancy ranges from 12 to 15 months, as current established treatments like surgical intervention, radiotherapy, and chemotherapy using temozolomide exhibit limited effectiveness. Beyond conventional approaches, the exploration of immunotherapy for glioblastoma treatment is underway. A methodology involves CAR-T cells, monoclonal antibodies, ADCC and nanobodies sourced from camelids. Immunotherapy ’s recent focal point is the cellular ligand B7-H3, notably abundant in tumor cells while either scarce or absent in normal ones. Its expression elevates with cancer progression and serves as a promising prognostic marker. In this article, we delve into the essence of B7-H3, elucidating its function and involvement in signaling pathways. We delineate the receptors it binds to and its significance in glioblastoma and other cancer types. Lastly, we examine its role in immunotherapy and the utilization of nanobodies in this domain.  \nKEYWORDS  \nglioblastoma, B7-H3, CD276, signaling pathways, immune checkpoints, immunotherapy  \n1 Introduction  \nCancer is a significant health issue, being a disease of considerable concern. In 2020, it was the second leading cause of death in the United States, with 602,350 deaths, following heart disease, which claimed 696,962 lives. It is noteworthy that cancer stands as a primary cause of death among women aged 40-59 years and both genders within the 60-79 year age range. While there has been a reduction in mortality rates for certain cancers such as leukemia, melanoma, and kidney cancer, it is important to mention that other cancers like glioblastoma continue to sustain their high fatality rates (1) .  \nGlioblastoma is the most common and malignant primary brain cancer. The World Health Organization (WHO) classifies glioblastoma as grade IV brain tumor. Currently  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \npatients with glioblastoma first undergo surgical resection which is followed by radiotherapy and chemotherapy with temozolomide (2). Despite the combinatorial treatment, 5-year survival rate is less than 10%(3) . Low survival rate of glioblastoma patients can be attr","cbCaifdj2uAky5Un","https://ap.wps.com/l/cbCaifdj2uAky5Un","pdf",2074777,21,"English","# Introduction\n# Glioblastoma, treatment limitations, and heterogeneity\n## Tumor microenvironment and blood-brain barrier\n## Immunotherapy approaches and clinical trial status\n# Nanotechnology and nanobodies\n## Advantages and potential BBB diffusion","[{\"question\":\"Why are current glioblastoma treatments limited in effectiveness?\",\"answer\":\"Despite combined surgical resection, radiotherapy, and temozolomide chemotherapy, outcomes remain poor, with 5-year survival below 10%. Key contributing factors include tumor heterogeneity, difficulty achieving complete resection, immune suppression in the tumor microenvironment, and blood-brain barrier–restricted drug delivery.\"},{\"question\":\"What is B7-H3 (CD276) and why is it important in glioblastoma?\",\"answer\":\"B7-H3 is a cellular ligand that is abundant in glioblastoma cells but scarce or absent in normal cells. Its expression increases with cancer progression and functions as a promising prognostic marker, making it a focal point for immunotherapy research.\"},{\"question\":\"How does the article connect B7-H3 biology to therapeutic strategies?\",\"answer\":\"It outlines B7-H3’s role in signaling pathways by describing the receptors it binds to. It then links this biology to immunotherapy development, including the use of nanobodies targeting B7-H3.\"}]","B7-H3 in glioblastoma and beyond: significance and therapeutic strategies | PDF",1789994354,53]