败血症
免疫抑制
免疫系统
医学
免疫学
重症监护医学
临床试验
内科学
作者
Mario Rienzo,Tomasz Skirecki,Guillaume Monneret,Jean François Timsit
标识
DOI:10.1080/13543784.2022.2102477
摘要
Introduction It is now well established that sepsis induces a state of acquired immunosuppression, with an increased risk of secondary infections that contributes to patients’ worsening. Thus, tackling sepsis-induced immunosuppression represents a promising perspective.Areas covered Of mechanisms responsible for sepsis-induced immunosuppression, the increased expression of co-inhibitory receptors such as PD-1, CTLA4, TIM-3, LAG-3, or BTLA and their ligands recently received considerable interest since their inhibition, thanks to the so-called checkpoint inhibitors (CPI), provided astonishing results in cancer by rebooting immune functions. This review reports on the first landmarks of these molecules in sepsis.Expert opinion Preclinical results are positive and the first human early phase clinical trials showed a beneficial effect on immunological functions and/or markers and suggested that tolerance of CPIs side effects, mainly auto-immune disorders, is acceptable in sepsis. Elsewhere, in some specific severe ICU infections such as fungal infections, preliminary convincing case reports have been published. Overall, the first results regarding CPIs in sepsis appear encouraging. However, further efforts are warranted, especially in defining the right patients to be treated (i.e. in an individualized approach) and establishing the optimal time to start an immune restoration. Larger trials are now mandatory to confirm CPIs’ potential in sepsis.
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