Vijay K. KUCHROO;Ana C. ANDERSON;Asaf MADI;Norio CHIHARA;Aviv REGEV;Meromit SINGER;The Brigham and Women's Hospital, Inc.;The Broad Institute, Inc.;Massachusetts Institute of Technology
发明人:
Vijay K. KUCHROO,Ana C. ANDERSON,Asaf MADI,Norio CHIHARA,Aviv REGEV,Meromit SINGER
申请号：
US15767074
公开号：
US20190255107A1
申请日:
2016.10.07
申请国别(地区):
US
年份:
2019
代理人:
摘要：
Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network as well as novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the co-expression of co-inhibitory receptors in dysfunctional T cells and identifies novel regulators of T cell dysfunction.
