PO.IM01.02 · 免疫学
靶向B7-H3以赋能精准肿瘤学的新型策略
Novel strategies for targeting B7-H3 to empower precision oncology
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
免疫检查点B7-H3（由CD276编码）是一种在多种癌症类型中新兴的免疫治疗靶点。然而，我们对B7-H3生物学、其失调及其在调控肿瘤微环境（TME）免疫和基质成分中作用的有限理解，阻碍了B7-H3靶向治疗的临床应用。通过利用基因工程小鼠模型和具有单细胞分辨率的多组学方法，我们确定B7-H3是在含有PTEN和TP53缺陷的癌症中最有前景的检查点免疫治疗靶点之一。除抑制T细胞外，我们还发现了B7-H3在调控TME中髓系细胞和基质细胞方面的非经典双重功能，从而促进癌症进展和治疗抵抗。在本研究中，我们回答了关于B7-H3信号及其在TME中细胞对应物的长期存在的问题，揭示了癌症治疗中B7-H3免疫治疗抵抗的细胞和分子基础，并开发了针对恶性肿瘤中B7-H3靶向免疫治疗的创新性、生物标志物驱动的联合策略。
查看英文原文 English abstract
Immune checkpoint B7-H3 (encoded by CD276) is an emerging immunotherapy target across diverse cancer types. However, our limited understanding of B7-H3 biology, its dysregulation, and its role in modulating immune and stromal components of the tumor microenvironment (TME) hinders the clinical application of B7-H3-targeting therapy. By leveraging genetically engineered mouse models and multi-omics approaches with single-cell resolution, we identified B7-H3 as one of the most promising checkpoint immunotherapy targets in cancers containing PTEN and TP53 defects. In addition to suppressing T cells, we identified non-canonical dual functions of B7-H3 in modulating myeloid and stromal cells in the TME, thereby promoting cancer progression and therapy resistance. In this study, we answered long-standing questions regarding B7-H3 signaling and its cellular counterpart in the TME, uncovered the cellular and molecular basis of resistance to B7-H3 immunotherapy in cancer treatment, and developed innovative biomarker-driven, combinatorial strategies for B7-H3-targeted immunotherapy in malignancies.
利益披露 Disclosure
D. Zhao, None.