Cancer and sepsis

Abstract

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.

Keywords: Cancer; Critical Care; Gut; Intensive Care; Sepsis; T cell.

Figure 1.. Lifetime Incidence Portrayal: Cancer, Sepsis and Mortality

(A)Lifetime incidence of developing cancer, (B) percentage of septic patients who have cancer, and (C) mortality of hospitalized patients with cancer and sepsis. Created with BioRender.com.

Figure 2. Pathophysiologic Insights: Sepsis, Cancer and the Immunologic Response.

Cancer (A) is a common and lethal disease. In the context of mortality from sepsis, risk varies significantly with cancer type, with pancreatic and lung cancer carrying the highest risk in solid tumors and hematologic malignancies also carrying a high risk. While ideally the immune system would robustly respond to a tumor, cancer cells can evade the immune system, allowing for a microenvironment that optimizes their survival and progression of cancer. Immune cells in the tumor microenvironment are also subjected to anti-inflammatory signals that decrease their effectiveness. The result is a maladaptive host response with increased exhaustion and decreased functionality in multiple immune cells. Sepsis (B) can be caused by a diverse array of microbes, including bacteria, fungi and viruses. Invading microbes lead to a host response, intended to contain the initiating infection. When this is unsuccessful, the host responsive can become maladaptive, resulting in cellular damage, ultimately leading to organ dysfunction. Cancer and sepsis (C) leads to higher mortality than sepsis in isolation and is responsible for a significant amount of mortality from cancer. Different tumor types are more susceptible to the development of sepsis, and the infections causing sepsis in cancer patients are more likely to be due anti-microbial resistant organisms. The presence of chronic immune dysfunction in cancer amplifies the acute dysregulated host response in sepsis, leading to increased organ dysfunction and elevated mortality. Created with BioRender.com.