IRF1 transcriptionally up-regulates CXCL10 which increases CD8⁺ T cells infiltration in colorectal cancer

Tumor-infiltrating CD8⁺ T cell is a robust predictor of outcome and immunotherapy response in patients with CRC. However, limited introduction of intratumoral CD8⁺ T cells remains a barrier for treatment of CRC. One of the most effective but difficult therapy for CD8⁺ T cells entering the tumor is activating chemokine receptors. This study observed a decrease in the expression level of interferon regulator factor 1(IRF1) in CRC tumor tissues compared to matched non-tumor tissues. Furthermore, it found a positive correlation between low IRF1 expression and unfavorable prognosis in CRC patients. The present study also demonstrated that overexpression of IRF1 attenuated tumor growth by promoting the accumulation of facilitating CD8⁺T cells at the tumor site in mouse models. Additionally, this study identified IRF1 response elements in the promoter region of CXCL10 and show that the binding of IRF1 promoted the transcription of CXCL10. Of note, it was discovered that an increase in CXCL10 was positively associated with improved survival in CRC. These findings strongly suggest that IRF1 serves as a key transcription factor for CXCL10, highlighting its potential as a therapeutic target for CRC.