Tbx21, also known as T-box transcription factor 21, is a crucial regulator in coordinating the immune response, especially the type 1 immune response [1,2,4]. It plays a vital role in various biological processes and diseases [1,2,3,4,5]. In the context of tumor progression, it has been associated with the regulation of cancer cell behavior [1,5].

In colorectal cancer (CRC), studies show that TBX21 expression is decreased in CRC tissues compared to normal tissue, and negatively correlated with CRC TNM stages [1,5]. Ectopic expression of TBX21 inhibits cell proliferation, promotes apoptosis, and suppresses metastasis in CRC cells both in vitro and in vivo [1,5]. RNA-seq and human phospho-kinase array assays revealed that ARHGAP29 acts as a target gene of TBX21, and TBX21 reduces the activation of kinases RSK and GSK3β [1]. Knockdown of TBX21 or ARHGAP29 abolishes these effects [1]. In the context of anti-PD-1 therapy in microsatellite stable CRC, Fusobacterium nucleatum can increase Tbx21 expression in CD8+ T cells, which transcriptionally represses PD-1, alleviating CD8+ T cell exhaustion and promoting effector function [2]. In CMS1 subtype CRC, high TBX21 expression and low methylation are associated with a survival advantage [3].

In summary, Tbx21 is essential for the type 1 immune response and has significant implications in CRC. The use of in vivo models in these studies has revealed its role in inhibiting CRC progression, providing potential targets for CRC therapy. Additionally, its role in immune-related processes in CRC, such as anti-PD-1 therapy response, highlights its importance in immunotherapy [1,2,3,5].

References:

1. Jiang, Xinyu, Du, Wenfei, Yang, Chenglong, Huang, Yongming, Shen, Wenzhi. 2023. TBX21 attenuates colorectal cancer progression via an ARHGAP29/RSK/GSK3β dependent manner. In Cellular oncology (Dordrecht, Netherlands), 46, 1269-1283. doi:10.1007/s13402-023-00809-6. https://pubmed.ncbi.nlm.nih.gov/37067748/

2. Wang, Xueliang, Fang, Yi, Liang, Wei, Sung, Joseph J Y, Yu, Jun. 2024. Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer. In Cancer cell, 42, 1729-1746.e8. doi:10.1016/j.ccell.2024.08.019. https://pubmed.ncbi.nlm.nih.gov/39303724/

3. Shen, Yuanyuan, Nussbaum, Yulia I, Manjunath, Yariswamy, Shyu, Chi-Ren, Mitchem, Jonathan B. 2022. TBX21 Methylation as a Potential Regulator of Immune Suppression in CMS1 Subtype Colorectal Cancer. In Cancers, 14, . doi:10.3390/cancers14194594. https://pubmed.ncbi.nlm.nih.gov/36230517/

4. Fatemi Langroudi, S R, Zeinaly, M, Ajamian, F. 2023. TBX21, the Master regulator of the type 1 immune response, overexpresses in the leukocytes of peripheral blood in patients with late-onset Alzheimer's disease. In Immunity & ageing : I & A, 20, 59. doi:10.1186/s12979-023-00385-1. https://pubmed.ncbi.nlm.nih.gov/37950255/

5. Yang, Xiaowen, Shen, Xinzhuang, Liu, Zongjun, Huang, Yongming, Shen, Wenzhi. 2025. TBX21 inhibits colorectal cancer metastasis through ARHGAP29/GSK3β inhibitory signaling- and MYCT1/ZO-1 signaling-dependent manner. In International journal of biological sciences, 21, 328-345. doi:10.7150/ijbs.97920. https://pubmed.ncbi.nlm.nih.gov/39744435/