Recent Advances of Precision Immunotherapy in Sepsis

Abstract Precision immunotherapy signifies the administration of the required type of immune intervention tailored to the state of immune activation at the appropriate time window. The classification of patients into the different states of immune activation is usually done by either a protein blood biomarker or a molecular blood endotype which is diagnostic of the precise immune state. Evidence coming from trials of the last decade suggests that immune interventions should be split into strategies aiming to attenuate the exaggerated immune responses, strategies aiming to restore sepsis-induced immunoparalysis (SII) and strategies aiming to restore the vascular tone. Suggested strategies to attenuate the immune responses are anakinra, nangibotide and tocilizumab. Biomarkers which guide their use are ferritin and sTREM-1 (soluble triggering receptor expressed on myeloid cells-1). Suggested strategies to restore SII are nivolumab, recombinant human interferon-gamma, CYT107 and GM-CSF (granulocyte macrophage colony stimulating factor). Biomarkers which guide their use are the expression of the human leukocyte antigen DR on blood monocytes, the absolute lymphocyte count, and blood levels of IgM. One recently suggested strategy to restore vascular tone is adrecizumab, the use is guided by the blood levels of bio-adrenomedulin. The use of these precision treatment strategies is still hampered by the need of large scale randomized controlled trials.