Recent advances of precision immunotherapy in sepsis

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 that 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, restore sepsis-induced immunoparalysis (SII) and restore the vascular tone. Suggested strategies to attenuate the immune responses are anakinra, nangibotide and tocilizumab. Biomarkers that guide their use are ferritin, soluble triggering receptor expressed on myeloid cells-1 and C-reactive protein. Suggested strategies to restore SII are nivolumab, recombinant human interferon-gamma, CYT107, granulocyte macrophage colony stimulating factor and IgM-enriched immunoglobulin prepapations. Biomarkers that guide their use are the expression of the human leukocyte antigen DR on blood monocytes, the absolute lymphocyte count and blood levels of immunoglobulin M. One recently suggested strategy to restore vascular tone is adrecizumab, the use of which is guided by blood levels of bio-adrenomedulin. The use of these precision treatment strategies is still hampered by the need for large-scale randomized controlled trials.