Tbx21, also known as T-Box Transcription Factor 21, is a crucial regulator in coordinating multiple aspects of the immune response, especially the type 1 immune response. It is involved in various biological processes and has significant implications for tumor progression [1,2,3,4].

In colorectal cancer (CRC), TBX21 expression is decreased compared to normal tissue and is negatively correlated with CRC TNM stages. Ectopic expression of TBX21 inhibits cell proliferation, promotes apoptosis, and suppresses metastasis in vitro and in vivo. RNA-seq and phospho-kinase array assays showed that ARHGAP29 is a target gene of TBX21, and TBX21 reduces the activation of kinase RSK and GSK3β. Knocking down TBX21 or ARHGAP29 abolishes the effects of TBX21 on cell proliferation, apoptosis, and RSK/GSK3β activation [1,4]. In microsatellite stable CRC, Fusobacterium nucleatum can induce Tbx21 promoter H3K27 acetylation and expression in CD8+ T cells by generating butyric acid, which transcriptionally represses PD-1, alleviating CD8+ T cell exhaustion [2]. In CMS1 subtype CRC, high TBX21 expression and low methylation are associated with a survival advantage, and TBX21 is related to enhanced CTL function [3].

In summary, Tbx21 plays a vital role in the immune response and tumor progression, especially in CRC. Functional studies, including those using gene-targeted models in vivo, have revealed its significance in regulating cell proliferation, apoptosis, and metastasis in CRC, as well as its role in immune-related processes in CRC. These findings suggest Tbx21 could be a potential target for CRC therapy and provide insights into immunotherapy in CRC [1,2,3,4].

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. 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/