TOX-Related T-Cell Exhaustion as a Link Between Chronic Inflammation, Tumor Immunity, and Immunotherapy A Bibliometric and Mechanism-Oriented Review.

Authors

Yun Cong, Ziwei Ma, Kai Zhong, Yaoqiang Bao, Shitao Lei, Pingping Qiao, Tuerganaili Aji, Yingmei Shao

Published in

Journal of inflammation research. Volume 19. Pages 638869. Epub Oct 14, 2026.

Abstract

Chronic inflammation and persistent antigen stimulation reshape T-cell fate and contribute to immune dysfunction in cancer, chronic infection, and inflammatory liver disease. TOX (TOX1) has emerged as a key transcriptional regulator linking these inflammatory contexts to T-cell exhaustion, immune checkpoint signaling, and immunotherapy response. However, existing reviews have mainly summarized molecular mechanisms and have not systematically connected the evolution of the field with its collaboration patterns, research hotspots, and emerging translational questions. A synthesis that combines bibliometric mapping with biological interpretation is needed to clarify how the field has evolved and where translational uncertainties remain.
Web of Science Core Collection, PubMed, and Embase were searched for TOX-related T-cell exhaustion studies published from 2010 to 2026. After deduplication and relevance screening, 180 publications were included. Bibliometric analyses were performed with bibliometrix, VOSviewer, and CiteSpace, and the resulting knowledge structures were interpreted through a mechanism-oriented narrative review.
Annual output increased markedly after the landmark TOX studies of 2019, reaching a peak in 2025. The field was highly concentrated: Frontiers in Immunology was the most productive venue, whereas Nature, Immunity, and Nature Immunology contained the most influential foundational papers. The USA and China dominated publication output, and their centrality scores were comparable (0.12 vs 0.13). However, their collaboration structures differed by partner distribution, with the USA more connected to high-output European partners and China contributing strongly to recent disease-focused translational work. Keyword and co-citation analyses converged on four themes: transcriptional programming, immune-checkpoint-associated dysfunction, tissue microenvironmental regulation, and translational intervention.
TOX-related T-cell exhaustion should not be interpreted only as a binary marker of dysfunctional immunity. Instead, it represents a context-dependent regulatory interface between chronic inflammation, antigen persistence, tumor immune suppression, and therapeutic resistance. This perspective is essential for developing next-generation immunotherapies that modulate, rather than simply reverse, T-cell exhaustion in inflammatory and malignant microenvironments.

PMID:
42894622
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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