Cancer immunotherapy has revolutionized the landscape of cancer treatment, particularly through the development of immune checkpoint blockade (ICB) targeting the PD-1/PD-L1 axis. However, the therapeutic efficacy of these interventions is frequently hindered by the immunosuppressive tumor microenvironment (TME), which is characterized by hypoxia, poor immune cell infiltration, and impaired antigen presentation. To overcome these barriers, MP-GCZ has been developed as a self-oxygenating biomimetic nanomotor to synergistically reprogram the TME and enhance antitumor immune responses through integrated multimodal mechanisms. This nanosystem combines photothermal therapy (PTT), cuproptosis-induced immunogenic cell death (ICD), and localized immune checkpoint modulation to address the complex immunosuppressive network of the TME. By leveraging a metal-organic framework scaffold, MP-GCZ enables controlled delivery of therapeutic components that alleviate hypoxia, trigger immunogenic tumor cell death, and enhance adaptive immune responses. When activated by near-infrared irradiation, MP-GCZ enhances dendritic cell maturation, increases infiltration of cytotoxic T lymphocytes, thereby transforming immunologically "cold" tumors into inflamed, immunogenic environments. Preclinical studies demonstrate that this strategy effectively suppresses both primary tumor growth and distant metastases, driven by systemic antitumor immunity. MP-GCZ represents a promising comprehensive approach to overcoming TME-mediated resistance and may offer a valuable solution to enhance the clinical efficacy of cancer immunotherapy.
Xin-yu Gu, Sheng-Wei Shen, Yuting He et al.· Materials Today Bio· 0 citations
RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing, constitute a dynamic epitranscriptomic network that profoundly regulates RNA metabolism and gene expression. Their dysregulation is increasingly recognized as a hallmark of cancer. This review critically synthesizes the multifaceted roles of RNA modifications to bridge the gap between descriptive epitranscriptomic mapping and functional tumor biology. We systematically evaluate how writers, readers, and erasers dictate transcript stability and translation efficiency, driving tissue-specific tumor evolution across diverse malignancies. Crucially, we explore the intersection of RNA modifications and the tumor immune microenvironment, detailing their mechanisms in orchestrating immune evasion, altering antigen presentation, and regulating immune checkpoints. Furthermore, we examine how epitranscriptomic reprogramming dictates cellular responses to chemotherapy, radiotherapy, targeted treatments, and immunotherapy. By comprehensively analyzing these mechanisms, this review aims to facilitate the translation of epitranscriptomic findings into clinical applications, laying a theoretical foundation for targeted anti-tumor strategies.
Cancer remains a major global health burden, with its incidence and mortality rates persistently high despite advances in treatment. Despite therapeutic innovations, malignant tumors continue to pose a formidable challenge to global health. Against this backdrop, the crosstalk between long non-coding RNAs (lncRNAs) and the Notch signaling pathway has emerged as a pivotal driver of tumorigenesis and progression. However, the complex regulatory network and a comprehensive mechanistic framework of this axis await systematic elucidation. This review systematically consolidates recent advances in understanding how lncRNAs precisely modulate Notch pathway activity through diverse mechanisms, including acting as competing endogenous RNAs, direct protein binding, epigenetic regulation, and exosome-mediated intercellular communication. The discussion encompasses various malignancies, spanning the digestive, respiratory, urogenital, nervous, and hematologic systems. The lncRNA-Notch regulatory axis is identified as a ubiquitous and functionally central oncogenic network. It orchestrates critical malignant phenotypes—such as such as stemness maintenance, epithelial-mesenchymal transition, metabolic shifts, drug resistance, and immune evasion—through intricate bidirectional crosstalk. Functional studies confirm that targeting key nodes of this axis can effectively reverse drug resistance and suppress tumor growth. Although challenges remain in its clinical translation, future research integrating single-cell multi-omics, nanotechnology, and other innovative strategies will undoubtedly open new avenues for precision diagnosis and cancer therapy.
Qing-miao Shi, Na Lou, Huiwu Xing et al.· Frontiers in Cell and Develo...· 0 citations