Targeting novel immune checkpoints in the B7-H family: advancing cancer immunotherapy from bench to bedsideLuo, Yuan, Liu
et alTrends Cancer (2025)
Abstract: The B7-H family of immune checkpoint molecules is a crucial component of the immune regulatory network for tumors, offering new opportunities to modulate the tumor microenvironment (TME). The B7-H family - which includes B7-H2 (inducible T cell costimulatory ligand, ICOSL), B7-H3, B7-H4, B7-H5 (V-domain immunoglobulin suppressor of T cell activation, VISTA), B7-H6, and B7-H7 (HHLA2) - is known for its diverse roles in regulating innate and adaptive immunity. These molecules can exhibit co-stimulatory or co-inhibitory effects on T cells, influencing processes such as T cell activation, differentiation, and effector functions, and they are involved in the recruitment and polarization of various immune cells. This review explores the structural characteristics, receptor-ligand interactions, and signaling pathways associated with each B7-H family member. We also discuss the family's impact on tumor immunity and potential therapeutic strategies.Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
Development of Antibody-Drug Conjugates for Malignancies of the Uterine Corpus: A ReviewYamanaka, Nishikawa, Yoshida
Cells (2025) 14 (5)
Abstract: Despite recent advances in cancer treatment, the prognosis for uterine malignancies (carcinoma and sarcoma) requires further improvement. Antibody-drug conjugates (ADCs) have emerged as a novel class of anti-cancer therapeutic agents, and multiple ADCs have been approved for other types of cancer. In 2024, trastuzumab deruxtecan received approval from the US Food and Drug Administration for cancer types and became the first ADC approved for the treatment of uterine malignancies. Many ADCs are currently being investigated in uterine malignancies, and therefore, there is a need to gain a deeper understanding of ADCs. In this article, we aim to provide a comprehensive overview of the advancements in ADCs. The contents of this article include the structure and mechanism of action, an analysis of recent clinical trials, and expected future clinical questions. This article also focuses on uterine sarcoma, which is not often highlighted as a target for ADC treatment.
A mini-overview of antibody-drug conjugates in platinum-resistant ovarian cancer: A preclinical and clinical perspectiveZhao, Yuan, Li
et alInt J Biol Macromol (2025) 304 (Pt 2), 140767
Abstract: Ovarian cancer is one of the most lethal gynaecologic cancers in China. Although platinum-based chemotherapy, PARP inhibitors and bevacizumab have prolonged long term survival and increased the overall response rate for platinum-sensitive ovarian cancer (PSOC), the treatment options for platinum-resistant ovarian cancer (PROC) are still limited. Antibody-drug conjugates (ADCs) represent a novel form of precision medicine, covalently linking specific monoclonal antibodies with potent cytotoxic payloads. Since mirvetuximab soravtansine (MIRV) received approval by the US Food and Drug Administration (FDA) as the first ADC for PROC in 2022, the development of novel ADCs for various targets in PROC has accelerated. In this review, we summarise the recent evidence and future prospects of ADCs targeting Folate Receptor alpha (FRα), mesothelin, cadherin-6, NaPi2b, human epidermal growth factor receptor 2 (HER2), dipeptidase 3 (DPEP3), B7-H4 (VTCN1), claudin-6 (CLDN6) and trophoblast antigen protein 2 (TROP2), in order to enhance our understanding of the clinical applications of ADCs and offer new insights for clinical practice and further research.Copyright © 2025. Published by Elsevier B.V.
Exploring B7-H4's role in prostate cancer dormancy post-androgen deprivation therapy: extracellular matrix interactions and therapeutic opportunitiesKang, Xue, Wong
et alMol Cancer Res (2025)
Abstract: Prostate cancer (PCa) is mainly managed with androgen deprivation therapy (ADT), but this often leads to a dormant state and subsequent relapse as lethal castration-resistant prostate cancer (CRPC). Using our unique PCa patient-derived xenograft (PDX) dormancy models, we investigated this critical dormant phase and discovered a selective increase in B7-H4 expression during the dormancy period following mouse host castration. This finding is supported by observations in clinical specimens of PCa patients treated with ADT. Differential expression analyses revealed the enrichment of extracellular matrix (ECM)-cell interaction pathways in B7-H4-positive cells. Functional assays demonstrated a crucial role of B7-H4 in maintaining dormancy within the ECM niche. Specifically, B7-H4 expression in LNCaP cells reduced proliferation within dormant ECM in vitro and significantly delayed relapse in castrated hosts in vivo. These results shed light on the dynamic regulation of B7-H4 during PCa dormancy and underscore its potential as a therapeutic target for preventing CRPC relapse. Implications: Our study identified membranous B7-H4 expression during ADT-induced dormancy, highlighting its potential as a therapeutic target for managing dormant prostate cancer and preventing fatal CRPC relapse.
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