Jul 2026· Immunology and Cell Biology· Vol 104, pp. 711 - 728· 0 citations· 200 references
Medicine
TL;DR
The mechanisms through which glioblastoma is initiated, localized, and eludes therapy responses are summarized and an update is provided on recent advances made within this therapeutic space to overcome GBM‐mediated immunosuppression.
Abstract
High‐grade central nervous system cancers incur a significant burden of care on society. The combination of therapeutic resistance and high mortality makes it both a challenging target and a devastating diagnosis. Of these, one in two is characterized as glioblastoma (GBM) with a median survival rate of only 13.5 months with the current standard of therapy. Modern interventions, such as PD‐1 and CTLA‐4 checkpoint inhibition and autologous CAR T cell delivery, remain stymied by both the difficult nature of drug delivery to the brain and the inherent immunosuppressive tumor microenvironment. However, recent advances in the characterization of GBM have unveiled promising new therapeutic avenues aiming to target and eliminate the tumor. In this review, we summarize the mechanisms through which GBM is initiated, localized, and eludes therapy responses and provide an update on recent advances made within this therapeutic space to overcome GBM‐mediated immunosuppression. We also discuss the challenges with current and next generational treatment strategies before finally exploring the landscape of potential future therapeutic targets.
Bladder cancer is a highly prevalent malignant tumor in the urinary system worldwide, and the treatment has been long facing significant challenges. Immunotherapy represented by PD-1 (programmed death receptor-1)/PD-L1 (programmed death ligand-1) inhibitors and targeted therapies such as antibody-drug conjugates have already changed the landscape. However, the efficacy of a single drug is limited, and the problem of drug resistance is quite prominent. The combined treatment strategy, through the deep synergy of pharmacology and immunology, aims to overcome tumor heterogeneity and immunosuppressive microenvironments. It has become a core research direction in the treatment of bladder cancer. This review systematically elaborates the synergistic biological mechanisms by which targeted drugs induce immunogenic cell death, re-adjust the tumor immune microenvironment, and immune checkpoint inhibitors amplify and prolong the therapeutic effect. It focuses on elaborating the groundbreaking clinical evidence achieved by the "ADC + immunotherapy" approach, such as ennozumab combined with pembrolizumab, in advanced first-line and neoadjuvant treatments, and also summarizes the emerging methods including dual immunotherapy combinations, immunotherapy combined with other regulators, and oncolytic viruses. Furthermore, this article thoroughly examines the challenges that may arise from combined treatment, such as the complexity of drug resistance mechanisms and the optimization of drug toxicity management. Finally, a series of prospects were presented regarding future directions such as the development of drugs targeting new targets in the tumor microenvironment. This article aims to provide an academic reference for a comprehensive understanding of the current status and future prospects of targeted and immunotherapy combined strategies for bladder cancer.
Zong-Hua Wang· International Journal of Bio...· 0 citations
Glioblastoma is one of the most aggressive primary brain tumors in adults. Despite intensive treatment, including surgery, radiotherapy, and chemotherapy using temozolomide, this type of tumor is characterized by rapid growth and development with subsequent complications. Due to the inefficiency of conventional treatment modalities, new effective targeted strategies need to be developed. The use of immune checkpoint inhibitors (ICIs) is an essential part of modern immunotherapy. The application of this drug has led to a fundamental shift in the treatment strategy of many advanced cancers because it can activate a natural immune reaction against tumor formation. Therefore, ICI is considered a new target for studying various types of oncological diseases. Nevertheless, in cases of glioblastoma, the efficacy of the therapy is reduced because of the immunosuppressive activity of the tumor microenvironment, low mutation frequency, and the blood-brain barrier. The paper considers the most common issues related to the use of ICIs in the treatment of glioblastoma and the prospective strategies that may improve the clinical picture of the disease. Special attention will be paid to the recent advances in combined treatment, alternative delivery pathways of ICIs used as adjuvant therapies, and the role of prognostic biomarkers. By combining immunotherapy with traditional clinical treatment methods and accurately screening the patients most likely to benefit, ICIS-based therapy is expected to provide new opportunities to prolong overall survival in patients with glioblastoma.
Weihao Tong· Theoretical and Natural Scie...· 0 citations
This review discusses the most recent progress in genetic therapies for gliomas, with a focus on clinical platforms and those nearing clinical translation.
Alexander F. Haddad, Rithvik Ramesh, J. Agudelo et al.· JAMA Neurology· 0 citations
The therapeutic landscape of targeted therapies in glioblastomas is summarized, spanning major target classes including receptor tyrosine kinases, intracellular signalling proteins, cell-cycle dysregulation and synthetic-lethal vulnerabilities and emerging strategies targeting genome integrity and telomeres, epigenetic modulators, and tumour-neural circuitry are examined.
E. Aquilanti, M. Touat, P. French et al.· Nature Reviews Clinical Onco...· 0 citations
Neuroblastoma (NB) is a pediatric cancer that develops from immature nerve cells in the peripheral sympathetic nervous system. NB is remarkably heterogeneous, ranging from spontaneous regression to aggressive progression, and is characterized by widespread dissemination and relapse. Approximately half of all NB patients present with widespread metastasis at diagnosis and are classified as high-risk with a substantial likelihood of treatment failure, despite receiving aggressive multimodal therapies, including surgery, chemotherapy, radiotherapy, autologous hematopoietic stem cell transplantation, and monoclonal antibody treatment. Beyond conventional multimodal approaches, immunotherapy has emerged as an essential part of cancer treatment, by boosting the immune system to recognize and eliminate tumor cells. In this review, we provide an overview of current therapeutic strategies for NB patients and summarize recent advances in the development of next-generation NB immunotherapies, highlighting their potential to improve NB management. We further discuss future directions for therapeutic improvement, and the potential limitations and challenges associated with translating these approaches into long-term benefits for NB patients.
Ke-En Tan, K. Yeo, Yat-Yuen Lim et al.· Cancer Biology and Medicine· 0 citations
IDH-wild-type glioblastoma (WHO CNS Grade IV; known as glioblastoma multiforme, GBM) is the most malignant and recurrent brain tumor in the central nervous system. Research on GBM primarily focuses on its mechanisms and immunotherapy. However, due to cold tumor characteristics such as the immunosuppressive tumor microenvironment (TME), blood-brain barrier (BBB) obstruction, and tumor heterogeneity, immunotherapy regimens remain in the clinical trial phase. Overcoming core challenges including BBB barrier, TME, and tumor proliferation, invasion, and migration is urgently needed. The review focuses on the molecular mechanism and comes up with target strategy. The core components in these JAK/STAT, RAGE pathway are one of most important and efficient sites which has a potential inhibiting GBM. In terms of strategy of sorting out BBB, CL5B targets claudin-5 to reversibly open BBB. Together with approaches such as the FG-PIC system, this strategy has demonstrated encouraging efficacy and provides a potential route to overcome BBB-associated drug resistance. Moreover, the combination of acriflavine and photodynamic therapy (PDT) increases CD8+T-cell infiltration by approximately 1.3-fold and markedly alleviates the immunosuppressive TME. These effects suggest a feasible strategy to address therapeutic resistance caused by both BBB limitation and TME-driven immune suppression. Overall, treatment strategies aimed at the “cold tumor” features of glioblastoma (GBM) offer new perspectives for GBM therapy.
Yun-Xi Yao· International Journal of Bio...· 0 citations
