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Programmed death-ligand 1 (PD-L1) carried by tumor-derived exosomes has emerged as a critical mediator of immune evasion and resistance to immune checkpoint blockade therapy. Unlike membrane-bound PD-L1, exosomal PD-L1 is systemically distributed and capable of suppressing T cell activity at distant sites. This review summarizes the current understanding of exosomal PD-L1 biogenesis, its immunosuppressive mechanisms, and its clinical relevance across multiple cancer types. We highlight its potential as a non-invasive biomarker for predicting therapeutic response and monitoring disease progression. Compared with tissue-based PD-L1 assessment, exosomal PD-L1 offers advantages in accessibility and dynamic reflection of tumor immune status. However, challenges remain regarding standardization of detection methods and clinical interpretation. Future directions include the integration of exosomal PD-L1 profiling into immunotherapy decision-making and the development of therapeutic strategies targeting exosome secretion. These insights may contribute to overcoming resistance in immunologically inert tumors and advancing precision oncology.
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http://dx.doi.org/10.3389/fimmu.2025.1603855 | DOI Listing |
Clin Transl Oncol
September 2025
Department of Basic Science, College of Medicine, Princess Nourah bint Abdulrahman, University, P.O.Box 84428, 11671, Riyadh, Saudi Arabia.
Esophageal cancer (EC) is one of the most serious health issues around the world, ranking seventh among the most lethal types of cancer and eleventh among the most common types of cancer worldwide. Traditional therapies-such as surgery, chemotherapy, and radiation therapy-often yield limited success, especially in the advanced stages of EC, prompting the pursuit of novel and more effective treatment strategies. Immunotherapy has emerged as a promising option; nonetheless, its clinical success is hindered by variable patient responses.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
August 2025
Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
Beta-glucans, naturally occurring polysaccharides derived from fungi, yeasts, cereals, and bacteria, have emerged as potent cancer therapeutics due to their multifaceted immunomodulatory, anti-inflammatory, and direct anti-tumor properties. These compounds engage pattern recognition receptors (PRRs) such as Dectin-1, Toll-like receptors (TLRs), and complement receptor 3 (CR3), activating macrophages, natural killer (NK) cells, and dendritic cells to enhance anti-tumor immunity. Beta-glucans suppress pro-inflammatory cytokines (e.
View Article and Find Full Text PDFCell Death Discov
August 2025
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Given the heterogeneity of the tumor microenvironment (TME), neoadjuvant immunotherapy combined with chemotherapy benefits only a subset of lung adenocarcinoma (LUAD) patients, and the mechanisms of resistance remain unclear. Transfer RNA-derived small RNAs (tsRNAs) are a new class of non-coding RNAs that participate in the remodeling of the TME. Using high-throughput small RNA microarray analysis, we found elevated expression of tsRNA 3'tiRNA-AlaCGC in tumors of LUAD patients resistant to neoadjuvant therapy, and negatively correlated with the poor prognosis in LUAD patients.
View Article and Find Full Text PDFDiscov Oncol
August 2025
Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China.
Objective: Tumor-derived exosomes testing can be effective in diagnosing disease and assisting in the treatment of disease. Our study utilizes bibliometric analysis to identify research hotspots related to tumor-derived exosomes, predict emerging research frontiers and development trends, and offer diverse perspectives for advancing research in this field.
Methods: Search the Web of Science Core Collection for English-language literature published on the field of tumor-derived exosomes from 2015 to 2024.
Adv Sci (Weinh)
August 2025
Department of Biological Sciences and Bioengineering, Inha University, Incheon, 22212, Republic of Korea.
A major challenge in immunotherapy is the inability to reliably predict patient responses due to the lack of robust biomarkers. Programmed cell death-ligand 1 (PD-L1)-expressing exosomes represent a promising biomarker candidate; however, existing detection platforms lack the sensitivity and specificity required for clinical translation. It is hypothesized that an avidity-based capture strategy utilizing dendrimer-mediated multivalent binding will effectively enhance molecular avidity and improve the selective capture of PD-L1-expressing exosomes.
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