| Literature DB >> 34101624 |
Yundong He1,2, Liguo Wang3, Ting Wei3, Yu-Tian Xiao4, Haoyue Sheng1,5,6, Hengchuan Su5,6, Daniel P Hollern7, Xiaoling Zhang8, Jian Ma1,5,6, Simeng Wen1, Hongyan Xie1, Yuqian Yan1, Yunqian Pan1, Xiaonan Hou9, Xiaojia Tang3, Vera J Suman3, Jodi M Carter10, Richard Weinshilboum11, Liewei Wang11, Krishna R Kalari3, Saravut J Weroha9, Alan H Bryce12, Judy C Boughey13, Haidong Dong2,14, Charles M Perou7, Dingwei Ye5,6, Matthew P Goetz9,15, Shancheng Ren4, Haojie Huang1,2,15.
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.Entities:
Keywords: Cancer; Cancer immunotherapy; Cell Biology; Molecular biology; Therapeutics
Year: 2021 PMID： 34101624 DOI： 10.1172/JCI147025
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808