Dr. Meier’s Research

Anesthesia and Sex Specific, Immune Dependent Impact on Cancer Progression

The importance of anesthetic choice during tumor surgery in light of its impact on patient survival is emphasized by emerging clinical data. Immune cell infiltration into developing cancers is considered a “hallmark of cancer”, as immune cells comprise a large part of the tumor mass and thus can critically influence tumor progression. The impact of anesthetics on various aspects of the immune system has been observed for decades but remains poorly understood, particularly in the context of cancer. Moreover, sex differences in the immune response to anesthetics have not been described even though male and female immune systems vary drastically. Understanding the interactions between anesthesia, the immune system, sex and cancer is therefore of critical importance to our specialty of anesthesiology as this may significantly impact our patients’ survival. Our preliminary data clearly demonstrate that isoflurane hastens melanoma growth in male mice only and does so in an immune dependent fashion. Our first aim is to demonstrate that not only tumor growth but also metastatic tendencies are impacted by isoflurane in a sex specific manner while our second aim proposes to investigate the role of sex hormones on the impact of volatile anesthesia on tumor progression. Our third aim proposes to investigate the direct effect of volatile anesthesia on fresh human immune cells and to compare male and female human cells with the murine system. Our overall goal is to better understand the impact of volatile anesthesia on our patients’ immune system and how this critically regulates cancer progression and survival. We hypothesize that men and women may be impacted differently due to vastly diverse immune systems. Our findings may significantly impact clinical practice by guiding anesthetic choice and administration during tumor related surgeries and by highlighting the consideration of sex when planning an anesthetic for cancer surgery.

Related Publications

Isoflurane Impacts Murine Melanoma Growth in a Sex-Specific, Immune-Dependent Manner: A Brief Report
Angela Meier, et al.

The impact of volatile anesthetics on cancer progression has been observed for decades, but sex differences have not been described. Male and female immune systems vary considerably, and the immune system plays an important role in limiting cancer growth. In the past, mouse models describing the impact of volatile anesthetics on cancer growth are limited to same-sex models. In this brief report, the authors describe a sex-specific impact of isoflurane on melanoma growth observed in wild-type, but not in immune-deficient mice. The authors recommend that future experimental designs related to anesthesia and cancer should evaluate the biological variable of sex in a systematic manner.

Inhibition of Human Neutrophil Extracellular Trap (NET) Production by Propofol and Lipid Emulsion
Angela Meier, et al.

Uncontrolled bacteremia is a common and life threatening condition that can lead to sepsis and septic shock with significant morbidity and mortality. Neutrophil granulocytes, the most abundant phagocytic leukocyte of the innate immune system, play an essential role in capturing and killing invading pathogens. Their antimicrobial repertoire includes the formation of Neutrophil Extracellular Traps (NETs), chromatin-based, web-like structures of DNA that facilitate the capture and killing of bacteria. In sepsis, however, it has been suggested that the uncontrolled release of NETs worsens disseminated coagulation and promotes venous thrombosis. In this study, the authors describe how clinically relevant concentrations of the commonly used sedative propofol as well as a lipid composition similar to the propofol carrier impair NET production by human neutrophils. Drugs commonly administered in the Intensive Care Unit (ICU) may impact the inflammatory response to either worsen or improve clinical outcomes and may therefore be considered for additional therapeutic effects if clinical studies confirm such findings.

Impact of Anesthetics on Human Neutrophil Function
Meier, Angela MD, PhD; Nizet, Victor MD

Anesthetics are widely used drugs administered in a multitude of clinical settings. Their impacts on various functions of the immune system have been studied but are still not fully understood. Neutrophil granulocytes are a critical first-line host defense mechanism against infections and contribute to the inflammatory phase of wound healing, but dysregulated neutrophil activation can also precipitate perioperative organ injury.  This review focused principally on studies performed using human neutrophils and close to realistic concentrations of anesthetics achieved in human plasma. Selected animal studies were included when they provided unique mechanistic insight and/or placed anesthetic effects on neutrophil function in an experimental disease context in vivo.

A better understanding of the interactions between common anesthetics and neutrophils may reveal considerations toward optimizing treatment of our most vulnerable patients in the intensive care unit and in the perioperative setting.  The authors recommend that future studies should be directed at fully elucidating the effect of anesthetics on neutrophil function and their comparative impact of patient outcome in relation to infection, sepsis, organ damage, and wound healing. If anesthetic effects at pharmacologically achieved concentrations will counteract or work in concert with other factors that perioperatively may impact immune function, such as surgical incision or overwhelming infection, is yet to be elucidated.