PhD, Moscow State University, Biochemistry and Biophysics
MS, Moscow State University, Biophysics and Physiology
Area(s) of Interest
Biochemistry and Immunopharmacology
The immediate focus of research is on cancer immunotherapy and prevention of iatrogenic complications due to elimination of the hypoxia-adenosinergic pathway.
A) Cancer immunotherapy is complementary to surgery, radiotherapy or chemotherapy. However, malignant cells can create a self-protective, tumor microenvironment (TME) that inhibits anti-tumor T cells. It is established that tumor cells are protected from anti-tumor T cells by the Hypoxia-Adenosinergic mechanism, which is triggered by very low local tumor tissue oxygen tension (i.e. hypoxia) and tumor hypoxia-produced extracellular adenosine. The key molecules of this immunosuppressive mechanism are a) cAMP-elevating A2A and, possibly, A2B adenosine receptors (A2AR/A2BR) and b) Hypoxia Inducible transcription Factor 1 alpha (HIF-1a). Preclinical testing suggests a promising novel approach that may prevent the inhibition of anti-tumor T cells and thereby improve the tumor rejection and cancer patients’ survival by eliminating the tumor protection by this Hypoxia-Adenosinergic mechanism.
B) While the Hypoxia-Adenosinergic tissue protection should be eliminated in order to enhance cancerous tissue destruction, it is a life saving mechanism when it protects normal tissues. It is shown that routinely and widely-used supplemental oxygen eliminates the Hypoxia-adenosinergic protection and thereby exacerbates acute lung inflammation. A novel supplemental oxygen protocol is suggested to allow safe oxygen without exacerbation of collateral inflammatory damage.
Prof. Sitkovsky is a joint appointment between the College of Science and the Bouvé College of Health Sciences.
113 Mugar Life Sciences Building
Immunophysiology researcher Michail Sitkovsky and his colleagues have found that supplemental oxygenation could dramatically increase the survival rate of patients with cancer. The breakthrough findings were published Wednesday in Science Translational Medicine.