Every year, one in ten adults in high-income countries undergoes surgery, and over 20% of patients over 45 having major abdominal surgery develop a hospital-acquired infection. For cancer patients, the risk of sepsis is ten times higher than for those without cancer, and postoperative sepsis is linked to cancer recurrence and higher long-term death rates. Current treatment is reactive—antibiotics given after infection appears. This research aims to change that by understanding why some patients become vulnerable in the first place. The researcher has already found that patients who later develop pneumonia show a specific pattern of immune activity in their blood, involving neutrophils—a type of white blood cell. This project will track how neutrophil populations change after surgery, then test their function: their ability to trap and kill bacteria, engulf pathogens, and influence T-cells. It will also test whether treatments that reverse T-cell dysfunction can restore normal immune responses. If successful, this work could lead to a precision-medicine strategy: identifying high-risk patients before infection strikes and intervening early, rather than waiting for antibiotics to fail. That would reduce postoperative sepsis, improve cancer survival, and cut the burden of hospital-acquired infections.
View original technical description
In high-income countries, 1 in 10 adults undergoes a surgical procedure each year. Over 20% of patients aged over 45 years undergoing major abdominal surgery develop nosocomial infections. Cancer resection forms the bulk of major surgical procedures in this cohort and importantly the risk of sepsis in patients with cancer is 10 times higher than those without. Retrospective data indicates that postoperative sepsis following major abdominal surgery was associated with cancer recurrence and increased long-term mortality. Unfortunately, current treatment of nosocomial infection is reactive and limited to antibiotic administration. Understanding of the immune changes following major abdominal surgery and their role in susceptibility to postoperative infection is evolving. My most recent paper analysing the perioperative whole-blood transcriptome has demonstrated an upregulation of neutrophil degranulation and myeloid-leucocyte-mediated immunity evident in those suffering a later postoperative pneumonia. I aim to build on these pilot data with this application by firstly exploring and phenotyping the temporal alterations in perioperative neutrophil populations. Then by the robust assessment of the functional status of these perioperative neutrophils; including their ability to produce neutrophil extracellular traps, phagocytose and their ability to alter T-cell function in the presence or absence of treatments designed to reverse T-cell dysfunction. The aim of this programme of research is ultimately to enable the development of a precision-medicine strategy for the prevention and management of post-operative nosocomial infections. Success in this highly prestigious grant would be a vital step in this research direction.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know