Immune checkpoints in sepsis: New hopes and challenges

Abstract

Sepsis is a life-threatening syndrome with a high incidence and a weighty economic burden. The cytokines storm in the early stage and the state of immunosuppression in the late stage contribute to the mortality of sepsis. Immune checkpoints expressed on lymphocytes and APCs, including CD28, CTLA-4, CD80, CD86, PD-1 and PD-L1, CD40 and CD40L, OX40 and OX40L, 4-1BB and 4-1BBL, BTLA, TIM family, play significant roles in the pathogenesis of sepsis through regulating the immune disorder. The specific therapies targeting immune checkpoints exhibit great potentials in the animal and preclinical studies, and further clinical trials are planning to implement. Here, we review the current literature on the roles played by immune checkpoints in the pathogenesis and treatment of sepsis. We hope to provide further insights into this novel immunomodulatory strategy.

Keywords:

• Checkpoints
• mechanisms
• sepsis
• state of immunosuppression
• therapy

Acknowledgments

We thank Professor Shu-Zhang Cui of the Emergency Department of Tianjin Medical University General Hospital for the guidance of review.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China (no. 81601714, 81871593). The funder had no role in study design, data collection and analysis, decision to publish, or manuscript preparation.