Photo of Simon C. Robson,  MB, ChB, FRCP, PhD

Simon C. Robson, MB, ChB, FRCP, PhD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 735-2921


srobson@bidmc.harvard.edu

Simon C. Robson, MB, ChB, FRCP, PhD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Charlotte F. and Irving W. Rabb Professor, Medicine, Harvard Medical School
  • Chief, GI/Liver, Beth Israel Deaconess Medical Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

Extracellular ATP, other nucleotides and adenosine play critical, albeit often opposing roles in inflammation, immune regulation and tumor cell biology. As an example, ATP is associated with direct induction of tumor cell death and functions as a danger-associated molecular pattern molecule (DAMP) leading to the activation of innate and adaptive immune responses mediated via type-2 purinergic receptors. Hence, ATP once released into the extracellular compartment might create an immune-stimulatory tumor microenvironment that would favor tumor immunity. ATP and other nucleotides are, however, catalyzed to nucleoside derivatives (e.g. adenosine) by the ectonucleotidases CD39 and CD73, resulting in the activation of type-1 purinergic or adenosine receptors. Adenosine will suppress innate and adaptive immune responses and would be expected to foster an immune-suppressive tumor microenvironment favoring tumor growth, as well as potentially inducing chemoresistance.

The concepts addressed by the Robson laboratory and others, is that modulating the purinergic balance within the tumor microenvironment to promote ATP effects over those of Ado (“immunogenic purinergic modulation” via inhibition of CD39 and CD73) might be expected to enhance chemotherapy induced cytotoxicity, via elicitation of robust and persistent anti-tumor immunity.

Publications

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  • Mascanfroni ID, Takenaka MC, Yeste A, Patel B, Wu Y, Kenison JE, Siddiqui S, Basso AS, Otterbein LE, Pardoll DM, Pan F, Priel A, Clish CB, Robson SC, Quintana FJ. Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-留. Nat Med 2015; 21:638-46. PubMed
  • Yoshida O, Dou L, Kimura S, Yokota S, Isse K, Robson SC, Geller DA, Thomson AW. CD39 deficiency in murine liver allografts promotes inflammatory injury and immune-mediated rejection. Transpl Immunol 2015; 32:76-83. PubMed
  • Roberts VS, Cowan PJ, Alexander SI, Robson SC, Dwyer KM. The role of adenosine receptors A2A and A2B signaling in renal fibrosis. Kidney Int 2014; 86:685-692. PubMed
  • Miao R, Luo H, Zhou H, Li G, Bu D, Yang X, Zhao X, Zhang H, Liu S, Zhong Y, Zou Z, Zhao Y, Yu K, He L, Sang X, Zhong S, Huang J, Wu Y, Miksad RA, Robson SC, Jiang C, Zhao Y, Zhao H. Identification of prognostic biomarkers in hepatitis B virus-related hepatocellular carcinoma and stratification by integrative multi-omics analysis. J Hepatol 2014. PubMed
  • Burnstock G, Vaughn B, Robson SC. Purinergic signalling in the liver in health and disease. Purinergic Signal. 2014; 10:51-70. PubMed
  • Lehwald N, Duhme C, Wildner M, Kuhn S, Fürst G, Forbes SJ, Jonas S, Robson SC, Knoefel WT, Schmelzle M, Schulte Am Esch J. HGF and SDF-1-mediated mobilization of CD133+ BMSC for hepatic regeneration following extensive liver resection. Liver Int 2013; 34:89-101. PubMed
  • Yoshida S, Kornek M, Ikenaga N, Schmelzle M, Masuzaki R, Csizmadia E, Wu Y, Robson SC, Schuppan D. Sublethal heat treatment promotes epithelial-mesenchymal transition and enhances the malignant potential of hepatocellular carcinoma. Hepatology 2014; 58:1667-80. PubMed
  • Mascanfroni ID, Yeste A, Vieira SM, Burns EJ, Patel B, Sloma I, Wu Y, Mayo L, Ben-Hamo R, Efroni S, Kuchroo VK, Robson SC, Quintana FJ. IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat Immunol 2013; 14:1054-63. PubMed
  • Eltzschig HK, Sitkovsky MV, Robson SC. Purinergic signaling during inflammation. N Engl J Med 2012; 367:2322-33. PubMed