To be, or not to be immunocompetent.

Several data support the view that impairment of the inflammatory-immune response is a hallmark of severe sepsis and the level and time of recovery to immunocompetence has a major impact on the clinical outcome of ICU patients. Recent studies demonstrate that improvement of anti-tumour immune response by targeting negative regulatory molecules, such as CD25, chronic T-lymphocyte activation antigen 4, and programmed death-1 receptor (PD-1)/PD-1 L, offers a novel opportunity to prevent or even reverse progression of tumour growth in experimental models and patients. Likewise, severe sepsis is associated with enhanced expression of those negative regulatory molecules, suggesting a novel approach to reverse immunoparalysis in sepsis. Consequently, targeting negative molecules in sepsis can reverse immunoparalysis and improve survival in experimental sepsis, as shown by Chang and colleagues in a recent issue of Critical Care. This opens new opportunities to overcome overwhelming downregulation of the adaptive immune response to prevent and/or improve recovery from sepsis.