# T-bet: biological functions, molecular mechanisms, and therapeutic applications: a systematic review

**Authors:** Xiaowen Yang, Min Sun, Xinyi Tang, Xiaoyuan Zhang, Wenzhi Shen

PMC · DOI: 10.3389/fimmu.2026.1671806 · Frontiers in Immunology · 2026-01-23

## TL;DR

This review explores T-bet's role in immune processes and diseases, highlighting its potential as a diagnostic and therapeutic target for cancer and immune disorders.

## Contribution

The paper systematically reviews T-bet's molecular mechanisms and clinical relevance across multiple diseases and tumor types.

## Key findings

- T-bet influences immune cell differentiation and contributes to autoimmune, infectious, and allergic diseases.
- T-bet is involved in tumor progression processes like proliferation, metastasis, and immune cell infiltration.
- T-bet shows potential as a prognostic marker and therapeutic target in various cancers.

## Abstract

T-bet is a transcription factor predominantly expressed in immune cells, and it has been associated with a range of physiological and pathological processes, including the differentiation of various immune cell types, the development of immune-related diseases, and tumor progression. Despite notable advancements in the field, current research on T-bet remains fragmented, primarily concentrating on functional studies within specific cell types or the progression of particular diseases. This review aims to provide a comprehensive synthesis of the most recent findings regarding the role of T-bet in various diseases, with an emphasis on elucidating its molecular mechanisms and potential clinical applications. We underscore the involvement of T-bet in the pathogenesis of systemic diseases, including autoimmune disorders, infectious diseases, allergic conditions, endocrine disorders, psychiatric illnesses, and chromosomal abnormalities. Furthermore, we summarize its role in the development of various malignant tumors, such as esophageal cancer, gastric cancer, breast cancer, colon cancer, prostate cancer, and hematological malignancies. Additionally, we discuss the impact of T-bet on several critical processes in tumor biology, including tumor cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), metastasis, immune cell infiltration, and iron-induced apoptosis. We also assess the potential of T-bet as a prognostic and therapeutic target for tumors. In conclusion, T-bet may serve as a significant biomarker for the diagnosis and treatment of immune disorders and cancer, as well as a target for innovative immunotherapeutic strategies aimed at addressing tumors and immune-related diseases.

## Linked entities

- **Genes:** TBX21 (T-box transcription factor 21) [NCBI Gene 30009]
- **Diseases:** esophageal cancer (MONDO:0007576), gastric cancer (MONDO:0001056), breast cancer (MONDO:0004989), colon cancer (MONDO:0002032), prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** TBX21 (T-box transcription factor 21) [NCBI Gene 30009] {aka IMD88, T-PET, T-bet, TBET, TBLYM}
- **Diseases:** immune disorders (MESH:D007154), prostate cancer (MESH:D011471), hematological malignancies (MESH:D019337), metastasis (MESH:D009362), systemic diseases (MESH:D034721), breast cancer (MESH:D001943), esophageal cancer (MESH:D004938), colon cancer (MESH:D015179), allergic conditions (MESH:D004342), psychiatric illnesses (MESH:D001523), endocrine disorders (MESH:D004700), autoimmune disorders (MESH:D001327), gastric cancer (MESH:D013274), chromosomal abnormalities (MESH:D002869), infectious diseases (MESH:D003141), cancer (MESH:D009369)
- **Chemicals:** iron (MESH:D007501)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12876164/full.md

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12876164/full.md

## References

152 references — full list in the complete paper: https://tomesphere.com/paper/PMC12876164/full.md

---
Source: https://tomesphere.com/paper/PMC12876164