Is T Cell Exhaustion a Treatable Trait in Sepsis?

TY - CHAP

T1 - Is T Cell Exhaustion a Treatable Trait in Sepsis?

AU - Fish, M.

AU - Swanson, C. M.

AU - Shankar-Hari, M.

PY - 2020/2/12

Y1 - 2020/2/12

N2 - The immune system is profoundly dysregulated in sepsis with simultaneous hyperinflammation and immunosuppression. One facet of sepsis-related immunosuppression is T cell exhaustion, which is characterized by impaired effector cell function and persistent upregulation of immune checkpoint inhibitory molecules such as programmed death molecule 1 (PD-1) and its ligand (PD-L1). T cell exhaustion increases the risk of adverse outcomes in sepsis patients. The ability to identify T cell exhaustion alongside the increase in risk of adverse events caused by this dysfunction makes it a treatable trait using immunostimulatory cytokines or monoclonal antibodies targeting these inhibitory molecules. Early phase trials in sepsis suggest that interleukin-7 or antibodies targeting PD-1 or PDL-1 are potential interventions to test in enriched sepsis populations. The knowledge gap to be addressed prior to late phase trials of these interventions includes the molecular basis of T cell exhaustion in sepsis and predictive markers for enriching sepsis trial populations.

AB - The immune system is profoundly dysregulated in sepsis with simultaneous hyperinflammation and immunosuppression. One facet of sepsis-related immunosuppression is T cell exhaustion, which is characterized by impaired effector cell function and persistent upregulation of immune checkpoint inhibitory molecules such as programmed death molecule 1 (PD-1) and its ligand (PD-L1). T cell exhaustion increases the risk of adverse outcomes in sepsis patients. The ability to identify T cell exhaustion alongside the increase in risk of adverse events caused by this dysfunction makes it a treatable trait using immunostimulatory cytokines or monoclonal antibodies targeting these inhibitory molecules. Early phase trials in sepsis suggest that interleukin-7 or antibodies targeting PD-1 or PDL-1 are potential interventions to test in enriched sepsis populations. The knowledge gap to be addressed prior to late phase trials of these interventions includes the molecular basis of T cell exhaustion in sepsis and predictive markers for enriching sepsis trial populations.

U2 - 10.1007/978-3-030-37323-8_22

DO - 10.1007/978-3-030-37323-8_22

M3 - Chapter

SN - 978-3-030-37323-8

SP - 271

EP - 279

BT - Annual Update in Intensive Care and Emergency Medicine 2020

A2 - Vincent, Jean-Louis

PB - Springer International Publishing

CY - Cham

ER -