GBM is the most common, aggressive, and intracranial primary brain tumor; it originates from the glial progenitor cells, has poor overall survival (OS), and has limited treatment options. In this decade, GBM immunotherapy is in trend and preferred over several conventional therapies, due to their better patient survival outcome. This review explores the clinical trials of several immunotherapeutic approaches (immune checkpoint blockers (ICBs), CAR T-cell therapy, cancer vaccines, and adoptive cell therapy) with their efficacy and safety. Despite significant progress, several challenges (viz., immunosuppressive microenvironment, heterogeneity, and blood-brain barrier (BBB)) were experienced that hamper their immunotherapeutic potential. Furthermore, these challenges were clinically studied to be resolved by multiple combinatorial approaches, discussed in the later part of the review. Thus, this review suggests the clinical use and potential of immunotherapy in GBM and provides the holistic recent knowledge and future perspectives.
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http://dx.doi.org/10.1016/j.lfs.2024.123018 | DOI Listing |
J Nanobiotechnology
December 2024
Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, the Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, 570102, China.
Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs.
View Article and Find Full Text PDFJ Control Release
December 2024
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China; National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China. Electronic address:
Glioblastoma-associated macrophages & microglia (GAMs) are critical immune cells within the glioblastoma (GBM) microenvironment. Their phagocytosis of GBM cells is crucial for initiating both innate and adaptive immune responses. GBM cells evade this immune attack by upregulating the anti-phagocytic molecule CD47 on their surface.
View Article and Find Full Text PDFImmunity
December 2024
Department of Neurosurgery, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address:
Whereas terminally exhausted T (Tex_term) cells retain anti-tumor cytotoxic functions, the frequencies of stem-like progenitor-exhausted T (Tex_prog) cells better reflect immunotherapeutic responsivity. Here, we examined the intratumoral cellular interactions that govern the transition to terminal T cell exhaustion. We defined a metric reflecting the intratumoral progenitor exhaustion-to-terminal exhaustion ratio (PETER), which decreased with tumor progression in solid cancers.
View Article and Find Full Text PDFDiscov Oncol
December 2024
Department of Gastroenterology, Second Affiliated Hospital, Nanjing Medical University, 121 Jiangjiayuan Road, Gulou District, Nanjing, Jiangsu, China.
Background: ZBTB11 is a putative transcription factor with an N-terminal BTB domain and tandem C-terminal zinc finger motifs. Recent studies have suggested a potential role for ZBTB11 in tumorigenesis. However, the biological significance of ZBTB11 in different cancer types remains uncertain.
View Article and Find Full Text PDFClin Transl Oncol
December 2024
Lillian S Wells Department of Neurosurgery at the University of Florida: University of Florida Lillian S Wells Department of Neurosurgery, Gainesville, FL, USA.
Glioblastoma (GBM) is one of the most common primary malignant brain tumors. Annually, there are about six instances recorded per 100,000 inhabitants. Treatment for GB has not advanced all that much.
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