Distinct lymphocyte immune signatures to nivolumab and recombinant IL-7 ex vivo in patients with sepsis.

Therapeutic modulation of sepsis-induced immune dysfunction by targeting lymphocyte dysfunction with recombinant IL-7 (rIL-7) and anti-PD-1 (e.g. nivolumab) has shown promise in preclinical and early clinical studies. Prior to conducting large randomized controlled trials, an in-depth understanding of the changes induced by rIL-7 or nivolumab (and their differences) in patients with sepsis is imperative. We performed a prospective observational cohort study including patients admitted to the intensive care unit with sepsis and characterized their T lymphocyte phenotype using flow cytometry. The ability of T lymphocytes to respond to a stimulus (using anti-CD3/CD28 beads) and the effect of rIL-7 or nivolumab on T lymphocyte immunophenotype ex vivo was assessed. In a cohort of 55 patients, CD4+ and CD8+ T lymphocyte PD-1 was higher and IL-7R lower compared with healthy volunteers. In a subset of 24 intensive care unit patients in whom in-depth immunophenotype was characterized, ex vivo response of lymphocytes to anti-CD3/CD28 beads was reduced compared with healthy volunteers, simultaneously inducing features consistent with immune activation and immunosuppression. rIL-7 was associated with a greater spectrum of changes compared with nivolumab. The response to rIL-7 and nivolumab was influenced by anti-CD3/CD28 bead costimulation. rIL-7 and nivolumab elicited distinct T lymphocyte responses ex vivo, and the changes were influenced by T lymphocyte activation. It needs to be determined if similar changes occur in vivo, which may influence the choice of immunomodulatory therapy in sepsis.