Pathogenesis of most chronic human diseases, including chronic infections, autoimmune diseases and cancers, often involves a persistent, unresolved inflammatory response. The molecular mechanisms that determine the co...Pathogenesis of most chronic human diseases, including chronic infections, autoimmune diseases and cancers, often involves a persistent, unresolved inflammatory response. The molecular mechanisms that determine the conversion of an acute inflammatory response into a chronic process had puzzled researchers for many years. Recent studies reveal that B7-H1 （CD274, PD-L1）, a newly identified co-stimulatory molecule, possesses dual functions of co-stimulation of naive T cells and inhibition of activated effector T cells. The aberrant cellular expression and deregulated function of B7-H1 have been reported during chronic viral and intracellular bacterial infection, as well as in many autoimmune diseases and cancers. Importantly, the deregulation of B7-H1＇s dual functions appears to be associated with a prolonged and incomplete immune response by luring naive T cells for activation and dampening activated effector T cells. Moreover, development of strategies targeting B7-H1 signals provides a new and promising approach to manipulate the devastating diseases associated with chronic inflammation. Thus, B7-H1 may play a critical immunoregulatory role in the chronicity of inflammatory responses. Cellular ＆ Molecular Immunology. 2006;3（3）：179-187.展开更多
After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human cancer.Much of the knowledge that led to recent breakthroughs seems quite logical from today...After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human cancer.Much of the knowledge that led to recent breakthroughs seems quite logical from today’s point of view.However,what we now cite as facts were originally considered paradoxes,meaning something contrary to expectations or perceived opinion at the time.In order to make gains in the field of immunotherapy,one had to be willing to confront ideas and concepts that seemed to contradict one another,and reconcile how each could be true.This is what led to new knowledge and advances.Here,we highlight some of these paradoxes and the milestone discoveries that followed,each one critical for our understanding of immune checkpoint pathways.By outlining some of the steps that we took and the challenges that we overcame,we hope to inspire and encourage future generations of researchers to confront the paradoxes that still permeate the field.展开更多
文摘Pathogenesis of most chronic human diseases, including chronic infections, autoimmune diseases and cancers, often involves a persistent, unresolved inflammatory response. The molecular mechanisms that determine the conversion of an acute inflammatory response into a chronic process had puzzled researchers for many years. Recent studies reveal that B7-H1 （CD274, PD-L1）, a newly identified co-stimulatory molecule, possesses dual functions of co-stimulation of naive T cells and inhibition of activated effector T cells. The aberrant cellular expression and deregulated function of B7-H1 have been reported during chronic viral and intracellular bacterial infection, as well as in many autoimmune diseases and cancers. Importantly, the deregulation of B7-H1＇s dual functions appears to be associated with a prolonged and incomplete immune response by luring naive T cells for activation and dampening activated effector T cells. Moreover, development of strategies targeting B7-H1 signals provides a new and promising approach to manipulate the devastating diseases associated with chronic inflammation. Thus, B7-H1 may play a critical immunoregulatory role in the chronicity of inflammatory responses. Cellular ＆ Molecular Immunology. 2006;3（3）：179-187.
基金Acknowledgements and conflicts of interestThe authors declare no conflicts of interest.
文摘After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human cancer.Much of the knowledge that led to recent breakthroughs seems quite logical from today’s point of view.However,what we now cite as facts were originally considered paradoxes,meaning something contrary to expectations or perceived opinion at the time.In order to make gains in the field of immunotherapy,one had to be willing to confront ideas and concepts that seemed to contradict one another,and reconcile how each could be true.This is what led to new knowledge and advances.Here,we highlight some of these paradoxes and the milestone discoveries that followed,each one critical for our understanding of immune checkpoint pathways.By outlining some of the steps that we took and the challenges that we overcame,we hope to inspire and encourage future generations of researchers to confront the paradoxes that still permeate the field.
