Tbx21, also known as T-Box Transcription Factor 21, is a crucial regulator of the immune response, especially the type 1 immune response [1,2,3,4,5,7]. It is involved in coordinating multiple aspects of the immune system, which has overall biological importance in maintaining immune homeostasis and responding to various pathogens and diseases.

In colorectal cancer (CRC), studies have shown that TBX21 expression is decreased in CRC tissues compared to normal tissue and is negatively correlated with CRC TNM stages [1,6]. Ectopic expression of TBX21 in vitro inhibits cell proliferation, promotes apoptosis, and reduces the activation of kinases RSK and GSK3β [1]. RNA-seq data indicates that ARHGAP29 is a target gene of TBX21 mediating downstream signaling activation [1]. In vivo xenograft model studies demonstrate that TBX21 inhibits colorectal tumor progression via the ARHGAP29/RSK/GSK3β signaling pathway [1]. Additionally, TBX21 inhibits CRC cell migration in vitro and metastasis in vivo through ARHGAP29/GSK3β inhibitory signaling-and MYCT1/ZO-1 signaling-dependent manners [6]. In microsatellite stable CRC, the pathogen Fusobacterium nucleatum generates butyric acid, which inhibits histone deacetylase 3/8 in CD8+ T cells, inducing Tbx21 promoter H3K27 acetylation and expression. TBX21 transcriptionally represses PD-1, alleviating CD8+ T cell exhaustion and promoting effector function, thus facilitating anti-PD-1 therapy [2]. In CMS1 subtype CRC, high TBX21 expression and low methylation are associated with a survival advantage, and TBX21 is associated with enhanced CTL function [3].

In conclusion, Tbx21 plays a vital role in the immune response and has significant implications in CRC. The findings from in vivo models such as xenograft models in CRC research have revealed its role in tumor progression and metastasis, as well as its potential as a therapeutic target. In addition, its role in modulating the immune response in the context of anti-PD-1 therapy in CRC further emphasizes its importance in cancer immunotherapy [1,2,3,6].