About this Research Topic
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Multiple organ failure resulting from sepsis is due to the cumulative dysfunction of cells constituting individual organs. Different types of cell death as the final result of cellular dysfunction have been proposed based on their morphological characteristics. In septic cell death, apoptosis (type I programmed cell death characterized by an orderly sequence of events like leaf abscission) and autophagy (type II programmed cell death) have attracted recent research interest.
Immunoparalysis in the subacute phase of sepsis is one of the harmful host responses that is challenging to address. In particular, T cell exhaustion leading to apoptosis is recognized as the pivotal pathway of immunoparalysis related to the immune checkpoint mechanism, e.g., programmed cell death 1 (PD-1) and its corresponding ligand 1 (PD-L1). Both types of cell death are thought to be associated with this subacute immunosuppressive phase of sepsis. A potential therapeutic approach to sepsis-induced immune suppression is to accelerate autophagy and thereby mitigate the apoptosis-induced immunosuppression. PD-1 and PD-L1 play a significant pathological role in immunoparalysis, not only in cancer but also in sepsis. Positive co-stimulatory pathways in T cells, such as CD28 signaling, permit the effector T cells to expand, resist sepsis-induced apoptosis, and clear pathogens. PD-1, on the other hand, activates inhibitory pathways on T cells and broadly enhances immunosuppressive signals across the innate and adaptive immune systems.
To countermeasure against this immunoparalysis, checkpoint blockade garners attention in clinical research on sepsis. As for clinical application, the immune checkpoint inhibitors for sepsis remain under scrutiny, but recent trials have been aborted.
In this Research Topic, we highlight updated approaches of immunotherapy using anti-PD-1 antibody and/or autophagy acceleration regarding crosstalk between apoptosis and autophagy in infectious diseases and share our future perspectives. The goal is to overcome the lack of scientific data on therapeutic efficacy, criteria for patient inclusion, and immune monitoring methodologies, which should be further improved in the immunotherapies for sepsis in clinical trials.
Topic Editor Eizo Watanabe received grant-in-aid for a collaborative project from Asahi Kasei Pharma Co., but declares no other Conflict Of Interest with regard to this Research Topic. Topic Editor Philip Efron has been a consultant for Aceragen, but declares no other Conflict Of Interest with regard to this Research Topic.
Immunoparalysis in the subacute phase of sepsis is one of the harmful host responses that is challenging to address. In particular, T cell exhaustion leading to apoptosis is recognized as the pivotal pathway of immunoparalysis related to the immune checkpoint mechanism, e.g., programmed cell death 1 (PD-1) and its corresponding ligand 1 (PD-L1). Both types of cell death are thought to be associated with this subacute immunosuppressive phase of sepsis. A potential therapeutic approach to sepsis-induced immune suppression is to accelerate autophagy and thereby mitigate the apoptosis-induced immunosuppression. PD-1 and PD-L1 play a significant pathological role in immunoparalysis, not only in cancer but also in sepsis. Positive co-stimulatory pathways in T cells, such as CD28 signaling, permit the effector T cells to expand, resist sepsis-induced apoptosis, and clear pathogens. PD-1, on the other hand, activates inhibitory pathways on T cells and broadly enhances immunosuppressive signals across the innate and adaptive immune systems.
To countermeasure against this immunoparalysis, checkpoint blockade garners attention in clinical research on sepsis. As for clinical application, the immune checkpoint inhibitors for sepsis remain under scrutiny, but recent trials have been aborted.
In this Research Topic, we highlight updated approaches of immunotherapy using anti-PD-1 antibody and/or autophagy acceleration regarding crosstalk between apoptosis and autophagy in infectious diseases and share our future perspectives. The goal is to overcome the lack of scientific data on therapeutic efficacy, criteria for patient inclusion, and immune monitoring methodologies, which should be further improved in the immunotherapies for sepsis in clinical trials.
Topic Editor Eizo Watanabe received grant-in-aid for a collaborative project from Asahi Kasei Pharma Co., but declares no other Conflict Of Interest with regard to this Research Topic. Topic Editor Philip Efron has been a consultant for Aceragen, but declares no other Conflict Of Interest with regard to this Research Topic.
Keywords: programmed cell death, sepsis, apoptosis, autophagy, immunotherapy, immune checkpoint inhibitors, clinical trial
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