@article{10.1172/JCI147025, author = {Yundong He AND Liguo Wang AND Ting Wei AND Yu-Tian Xiao AND Haoyue Sheng AND Hengchuan Su AND Daniel P. Hollern AND Xiaoling Zhang AND Jian Ma AND Simeng Wen AND Hongyan Xie AND Yuqian Yan AND Yunqian Pan AND Xiaonan Hou AND Xiaojia Tang AND Vera J. Suman AND Jodi M. Carter AND Richard Weinshilboum AND Liewei Wang AND Krishna R. Kalari AND Saravut J. Weroha AND Alan H. Bryce AND Judy C. Boughey AND Haidong Dong AND Charles M. Perou AND Dingwei Ye AND Matthew P. Goetz AND Shancheng Ren AND Haojie Huang}, journal = {The Journal of Clinical Investigation}, publisher = {The American Society for Clinical Investigation}, title = {FOXA1 overexpression suppresses interferon signaling and immune response in cancer}, year = {2021}, month = {7}, volume = {131}, url = {https://www.jci.org/articles/view/147025}, abstract = {Androgen receptor–positive prostate cancer (PCa) and estrogen receptor–positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients. FOXA1 bound the STAT2 DNA-binding domain and suppressed STAT2 DNA-binding activity, IFN signaling gene expression, and cancer immune response independently of the transactivation activity of FOXA1 and its mutations detected in PCa and BCa. Increased FOXA1 expression promoted cancer immuno- and chemotherapy resistance in mice and PCa and BCa patients. These findings were also validated in bladder cancer expressing high levels of FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal PCa, BCa, and bladder cancer to immuno- and chemotherapy.}, number = {14}, doi = {10.1172/JCI147025}, url = {https://doi.org/10.1172/JCI147025}, }