Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.
Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.
Clin Sci (Lond). 2023 Jun 14;137(11):881-893. doi: 10.1042/CS20220713.
Sepsis is one of the leading causes of death worldwide. While mortality is high regardless of inciting infection or comorbidities, mortality in patients with cancer and sepsis is significantly higher than mortality in patients with sepsis without cancer. Cancer patients are also significantly more likely to develop sepsis than the general population. The mechanisms underlying increased mortality in cancer and sepsis patients are multifactorial. Cancer treatment alters the host immune response and can increase susceptibility to infection. Preclinical data also suggests that cancer, in and of itself, increases mortality from sepsis with dysregulation of the adaptive immune system playing a key role. Further, preclinical data demonstrate that sepsis can alter subsequent tumor growth while tumoral immunity impacts survival from sepsis. Checkpoint inhibition is a well-accepted treatment for many types of cancer, and there is increasing evidence suggesting this may be a useful strategy in sepsis as well. However, preclinical studies of checkpoint inhibition in cancer and sepsis demonstrate results that could not have been predicted by examining either variable in isolation. As sepsis management transitions from a 'one size fits all' model to a more individualized approach, understanding the mechanistic impact of cancer on outcomes from sepsis represents an important strategy towards delivering on the promise of precision medicine in the intensive care unit.
脓毒症是全球主要的死亡原因之一。无论感染原因或合并症如何,死亡率都很高,但癌症和脓毒症患者的死亡率明显高于没有癌症的脓毒症患者。癌症患者发生脓毒症的几率也明显高于一般人群。癌症和脓毒症患者死亡率增加的机制是多方面的。癌症治疗改变了宿主的免疫反应,并可能增加感染的易感性。临床前数据还表明,癌症本身就会增加脓毒症的死亡率,适应性免疫系统的失调起着关键作用。此外,临床前数据表明,脓毒症可以改变随后的肿瘤生长,而肿瘤免疫会影响脓毒症的生存。检查点抑制是许多类型癌症的一种公认的治疗方法,越来越多的证据表明,它在脓毒症中也是一种有用的策略。然而,癌症和脓毒症中检查点抑制的临床前研究结果表明,如果单独检查任何一个变量,都无法预测这些结果。随着脓毒症管理从“一刀切”的模式向更个体化的方法转变,了解癌症对脓毒症结局的机制影响代表了在重症监护病房实现精准医学承诺的重要策略。