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

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 immunostimulatory tumor microenvironment that would promote tumor death. ATP and other nucleotides are, however, catalyzed to nucleoside derivatives (e.g. adenosine) by the ectonucleotidases CD39 family members and CD73, resulting in the activation of type-1 purinergic or adenosine receptors.

Adenosine as an immune checkpoint mediator will suppress innate and adaptive immune responses and would be expected to foster an immunosuppressive tumor microenvironment favoring tumor growth, as well as potentially inducing chemoresistance.

The concepts, addressed by the Robson laboratory and others, are that modulating the purinergic balance within the tumor microenvironment to promote ATP effects over those of adenosine (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.

See: Immunological Reviews 2017; 276: 121–144.

Publications

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  • Correa-Costa M, Gallo D, Csizmadia E, Gomperts E, Lieberum JL, Hauser CJ, Ji X, Wang B, Câmara NOS, Robson SC, Otterbein LE. Carbon monoxide protects the kidney through the central circadian clock and CD39. Proc Natl Acad Sci U S A 2018; 115:E2302-E2310. PubMed
  • Hirata Y, Furuhashi K, Ishii H, Li HW, Pinho S, Ding L, Robson SC, Frenette PS, Fujisaki J. CD150Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine. Cell Stem Cell 2018; 22:445-453.e5. PubMed
  • Kishore BK, Robson SC, Dwyer KM. CD39-adenosinergic axis in renal pathophysiology and therapeutics. Purinergic Signal. 2018. PubMed
  • Wang A, Wu L, Lin J, Han L, Bian J, Wu Y, Robson SC, Xue L, Ge Y, Sang X, Wang W, Zhao H. Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma. Nat Commun 2018; 9:894. PubMed
  • Zhong AH, Gordon Jiang Z, Cummings RD, Robson SC. Various N-glycoforms differentially upregulate E-NTPDase activity of the NTPDase3/CD39L3 ecto-enzymatic domain. Purinergic Signal. 2017. PubMed
  • Savio LEB, de Andrade Mello P, Figliuolo VR, de Avelar Almeida TF, Santana PT, Oliveira SDS, Silva CLM, Feldbrügge L, Csizmadia E, Minshall RD, Longhi MS, Wu Y, Robson SC, Coutinho-Silva R. CD39 Limits P2X7 Receptor Inflammatory Signaling and Attenuates Sepsis-Induced Liver Injury. J Hepatol 2017. PubMed
  • Allard B, Longhi MS, Robson SC, Stagg J. The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets. Immunol Rev 2017; 276:121-144. PubMed
  • Atanasov G, Dietel C, Feldbrügge L, Benzing C, Krenzien F, Brandl A, Mann E, Englisch JP, Schierle K, Robson SC, Splith K, Morgul MH, Reutzel-Selke A, Jonas S, Pascher A, Bahra M, Pratschke J, Schmelzle M. Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma. Oncoimmunology 2017; 6:e1331806. PubMed
  • Longhi MS, Vuerich M, Kalbasi A, Kenison JE, Yeste A, Csizmadia E, Vaughn B, Feldbrugge L, Mitsuhashi S, Wegiel B, Otterbein L, Moss A, Quintana FJ, Robson SC. Bilirubin suppresses Th17 immunity in colitis by upregulating CD39. JCI Insight 2017. PubMed
  • Atanasov G, Schierle K, Hau HM, Dietel C, Krenzien F, Brandl A, Wiltberger G, Englisch JP, Robson SC, Reutzel-Selke A, Pascher A, Jonas S, Pratschke J, Benzing C, Schmelzle M. Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma. Ann Surg Oncol 2016. PubMed
  • Atanasov G, Hau HM, Dietel C, Benzing C, Krenzien F, Brandl A, Englisch JP, Wiltberger G, Schierle K, Robson SC, Reutzel-Selke A, Jonas S, Pascher A, Pratschke J, Schmelzle M. Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma. J Surg Oncol 2016. PubMed
  • Gupta PK, Godec J, Wolski D, Adland E, Yates K, Pauken KE, Cosgrove C, Ledderose C, Junger WG, Robson SC, Wherry EJ, Alter G, Goulder PJ, Klenerman P, Sharpe AH, Lauer GM, Haining WN. CD39 Expression Identifies Terminally Exhausted CD8+ T Cells. PLoS Pathog. 2015; 11:e1005177. PubMed
  • 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-α. 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
  • Atanasov G, Hau HM, Dietel C, Benzing C, Krenzien F, Brandl A, Wiltberger G, Matia I, Prager I, Schierle K, Robson SC, Reutzel-Selke A, Pratschke J, Schmelzle M, Jonas S. Prognostic significance of macrophage invasion in hilar cholangiocarcinoma. BMC Cancer 2015; 15:790. 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
  • 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; 86:685-92. 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
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