CaNCURE Mentors


Michail Sitkovsky, Ph.D.


Professor and Chair of Immunophysiology and Pharmaceutical Biotechnology
Northeastern University




m.sitkovsky@neu.edu

Biography: Dr. Sitkovsky received his Ph.D. in biophysics and physiology at Moscow State University in 1973. In 1974, he learned about the paradoxical coexistence of tumor and anti-tumor immune cells in the same cancer patient and has been trying to solve this problem ever since. He studied molecular mechanisms of lymphocyte activation in Moscow State University (1970-1981) and at the MIT Center for Cancer Research (1981-1984) first as a postdoctoral fellow with professor Hermann Eisen and then as the research scientist. After 20 years of research of cytotoxic T lymphocytes regulation in normal, inflamed, and cancerous tissues in the Biochemistry and Immunopharmacology Section, Laboratory of Immunology, NIAID, NIH (1984-2004) he moved back to Boston and founded the New England Inflammation and Tissue Protection Institute, a Consortium at Northeastern University. His main interests are to further understand the subtleties of regulation of T cells by the immunosuppressive Hypoxia-Adenosinergic pathway and in “engineering inflammation” by recruiting this pathway to prevent autoimmunity or to weaken the Hypoxia-Adenosinergic protection of tumors from anti-tumor T cells.

Research and Expertise: 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.

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