Neutrophils are the most abundant population of white blood cells in the circulation that play a key role in the innate immune system responses. In the past, these cells were viewed as merely dedicated to phagocytosis and the production of reactive oxygen species (ROS). Nowadays, they are recognized for their extreme versatility with regard to function and as important players influencing tumor development. Neutrophils are major effectors of acute inflammation, but also contribute to chronic inflammatory conditions and adaptive immune responses.
Inflammation has been associated with increased susceptibility for cancer. Neutrophils, as a crucial component of this process, play essential role in inflammation-driven tumorigenesis therefore representing an independent prognostic marker in a broad variety of neoplasias. Depending on the cytokine milieu in the tumor microenvironment, tumor infiltrating neutrophils (TANs) appear to have diverse phenotypes i.e. tumor promoting (N2) or inhibiting (N1). Importantly, alterations in neutrophil differentiation could be responsible for the changes in the host predisposition for tumor development, since these cells have a capacity to influence tumor angiogenesis, growth and metastasis.
Our research group focuses on the neutrophil-dependent immunoregulatory mechanisms that are responsible for the cancerogenesis in mice and human. We study the molecular mechanisms involved in neutrophil polarization, mobilization and activation. Our ultimate aim is to identify effective therapeutic approaches to target tumor- promoting neutrophil functions.
Moreover, we are interested in overall neutrophil biology, i.e. development, differentiation, activation, migration and responses to various inflammatory stimuli in disease. We analyze the role of multiple cytokines and growth factors in the regulation of emergency myelopoiesis, factors involved in neutrophil homing and the correlation between neutrophil activation and the outcome of disease.
Elena Siakaeva (MD)