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Background: T-cell exhaustion (Tex) represents a distinct immunological state characterized by the progressive functional deterioration of T cells under persistent antigenic stimulation. In recent years, the field of Tex research has attracted considerable attention, accompanied by a dramatic surge in related scientific literature. This study employed bibliometric methods to conduct a comprehensive analysis of Tex-related publications.
Methods: The scientific literature focusing on Tex published between 2005 and 2024 was retrieved from the Web of Science Core Collection. For comprehensive bibliometric evaluation, tools including CiteSpace, VOSviewer, and online websites were used to construct visual networks, including co-authorship, co-citation, and co-occurrence analysis. Quantitative assessment of research output and impact was performed through multiple metrics.
Results: The analysis included a total of 2831 publications. The data fitting analysis indicated an exponential growth in the number of publications per year. Regarding research contributions, the United States and China have consistently demonstrated their leading positions. Among academic institutions and individual researchers, Harvard University has emerged as the most productive organization. Reference analysis showed that chimeric antigen receptor (CAR) T-cell therapy is one of the fields that attract greatest attention in the current Tex research. Keyword analysis revealed that cancer was the most studied disease in this area, followed by hepatocellular carcinoma and HIV. Analysis of high-frequency keywords also found that current research focuses on the field centered around immunotherapy and immune checkpoint inhibitors, functional status of T cells and the mechanisms underlying Tex, tumor microenvironment, prognosis and biomarkers, and the role of Tex in specific diseases. In addition, in the coming years, several key areas will remain at the forefront of scientific exploration. These include machine learning, pan-cancer, programmed death-1 blockade, scRNA-seq, immune tolerance, VISTA, immunotherapy resistance, exosome, chronic inflammation, gene editing, triple-negative breast cancer, tumor microenvironment, solid tumors, multiple myeloma, and extracellular vesicles.
Conclusions: This research represents the inaugural effort to perform an extensive bibliometric evaluation of literature focusing on Tex between 2005 and 2024. The findings derived from this analysis offer a credible resource for scholars aiming to swiftly grasp essential insights and emerging trends, as well as future hotspots within this domain.
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http://dx.doi.org/10.1245/s10434-025-18066-2 | DOI Listing |
Nat Cell Biol
September 2025
NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, China.
The colon exhibits higher propensity for tumour development than ileum. However, the role of immune microenvironment differences in driving this disparity remains unclear. Here, by comparing paired ileum and colon samples from patients with colorectal cancer (CRC) and healthy donors, we identified ileum-enriched CD160CD8 T cells with previously unrecognized characteristics, including resistance to terminal exhaustion and strong clonal expansion.
View Article and Find Full Text PDFBiomaterials
September 2025
Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address:
The stimulator of interferon genes (STING) pathway represents a promising target in cancer immunotherapy. However, the clinical translation of cyclic dinucleotide (CDN)-based STING agonists remains hindered by insufficient formation of functional CDN-STING complexes. This critical bottleneck arises from two interdependent barriers: inefficient cytosolic CDN delivery and tumor-specific STING silencing via DNA methyltransferase-mediated promoter hypermethylation.
View Article and Find Full Text PDFJ Clin Invest
September 2025
State Key Laboratory of Molecular Oncology, National Cancer Center/National, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Pancreatic cancer (PC) is notoriously resistant to both chemotherapy and immunotherapy, presenting a major therapeutic challenge. Epigenetic modifications play a critical role in PC progression, yet their contribution to chemoimmunotherapy resistance remains poorly understood. Here, we identified the transcription factor ZEB1 as a critical driver of chemoimmunotherapy resistance in PC.
View Article and Find Full Text PDFBiotechnol J
September 2025
Department of Biochemical Engineering, University College London, London, UK.
Chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated clinical efficacy in treating haematological malignancies, resulting in multiple regulatory approvals. However, there is a need for robust manufacturing platforms and the use of GMP-aligned reagents to meet the clinical and commercial demands. This study investigates the impact of serum/xeno-free medium (SXFM) and cytokine supplementation on CAR-T cell production in static and agitated culture systems, using 24-well plate G-Rex vessels and 500 mL stirred tank bioreactors (STRs), respectively.
View Article and Find Full Text PDFOncol Lett
November 2025
Service of Immunology, University Hospital 'José Eleuterio González', Autonomous University of Nuevo León, Monterrey, Nuevo León 64460, Mexico.
Clear cell renal cell carcinoma (ccRCC) is a neoplastic disease associated with poor prognosis. Localized disease is successfully treated with nephrectomy; however, advanced disease often requires the combined use of immunotherapy and targeted therapy. To the best of our knowledge, there is no validated method to predict immunotherapy response and there is a lack of knowledge regarding the expression kinetics of exhaustion receptors in the early stages of ccRCC.
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