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

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

Beth Israel Deaconess Medical Center


  • Charlotte F. and Irving W. Rabb Professor, Medicine, Harvard Medical School


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 from Harvard Catalyst Profiles

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  • Tiwari-Heckler S, Yee EU, Yalcin Y, Park J, Nguyen DT, Gao W, Csizmadia E, Afdhal N, Mukamal KJ, Robson SC, Lai M, Schwartz RE, Jiang ZG. Adenosine deaminase 2 produced by infiltrative monocytes promotes liver fibrosis in nonalcoholic fatty liver disease. Cell Rep 2021; 37:109897. PubMed
  • Whitley MJ, Suwanpradid J, Lai C, Jiang S, Cook JL, Zelac DE, Rudolph R, Corcoran DL, Degan S, Spasojevic I, Levinson H, Erdmann D, Reid C, Zhang JY, Robson SC, Healy E, Havran WL, MacLeod AS. ENTPD1(CD39) expression inhibits ultraviolet radiation-induced DNA damage repair via purinergic signaling and is associated with metastasis in human cutaneous squamous cell carcinoma. J Invest Dermatol 2021. PubMed
  • Bareche Y, Pommey S, Carneiro M, Buisseret L, Cousineau I, Thebault P, Chrobak P, Communal L, Allard D, Robson SC, Mes-Masson AM, Provencher D, Lapointe R, Stagg J. High-dimensional analysis of the adenosine pathway in high-grade serous ovarian cancer. J Immunother Cancer 2021. PubMed
  • Longhi MS, Feng L, Robson SC. Targeting ectonucleotidases to treat inflammation and halt cancer development in the gut. Biochem Pharmacol 2021. PubMed
  • Pereira M, Lee NT, Noonan J, Willcox AEH, Calvello I, Georgy SR, Selan C, Chia JS, Hauw W, Wang X, Peter K, Robson SC, Nandurkar HH, Sashindranath M. Early Endothelial Activation in a Mouse Model of Graft vs Host Disease Following Chemotherapy. 2021; 12:708554. PubMed
  • Kakiuchi M, Hirata Y, Robson SC, Fujisaki J. Paradoxical regulation of allogeneic bone marrow engraftment and immune privilege by mesenchymal cells and adenosine: Differential effect of mesenchymal cell and Treg. Biol Blood Marrow Transplant 2020. PubMed
  • Dwyer KM, Kishore BK, Robson SC. Conversion of extracellular ATP into adenosine: a master switch in renal health and disease. Nat Rev Nephrol 2020; 16:509-524. PubMed
  • Kakiuchi M, Hirata Y, Robson SC, Fujisaki J. Transfer of stem cell niche-residential regulatory T cells prevents post-irradiation bone marrow injury. Haematologica 2020. PubMed
  • Savio LEB, de Andrade Mello P, Santos SACS, de Sousa JC, Oliveira SDS, Minshall RD, Kurtenbach E, Wu Y, Longhi MS, Robson SC, Coutinho-Silva R. P2X7 receptor activation increases expression of caveolin-1 and formation of macrophage lipid rafts, thereby boosting CD39 activity. J Cell Sci 2020. PubMed
  • Yan J, Li XY, Roman Aguilera A, Xiao C, Jacoberger-Foissac C, Nowlan B, Robson SC, Beers C, Moesta AK, Geetha N, Teng MWL, Smyth MJ. Control of Metastases via Myeloid CD39 and NK Cell Effector Function. Cancer Immunol Res 2020; 8:356-367. PubMed
  • Meyer AV, Klein D, de Leve S, Szymonowicz K, Stuschke M, Robson SC, Jendrossek V, Wirsdörfer F. Host CD39 Deficiency Affects Radiation-Induced Tumor Growth Delay and Aggravates Radiation-Induced Normal Tissue Toxicity. 2020; 10:554883. PubMed
  • Savio LEB, de Andrade Mello P, Santos SACS, de Sousa JC, Oliveira SDS, Minshall RD, Kurtenbach E, Wu Y, Longhi MS, Robson SC, Coutinho-Silva R. P2X7 receptor activation increases caveolin-1 expression and macrophage lipid raft formation boosting CD39 activity. J Cell Sci 2020. PubMed
  • Li XY, Moesta AK, Xiao C, Nakamura K, Casey M, Zhang H, Madore J, Lepletier A, Aguilera AR, Sundarrajan A, Jacoberger-Foissac C, Wong C, Dela Cruz T, Welch M, Lerner AG, Spatola BN, Soros VB, Corbin J, Anderson AC, Effern M, Hölzel M, Robson SC, Johnston RL, Waddell N, Smith C, Bald T, Geetha N, Beers C, Teng MWL, Smyth MJ. Targeting CD39 in Cancer Reveals an Extracellular ATP- and Inflammasome-Driven Tumor Immunity. 2019; 9:1754-1773. PubMed
  • Hao Y, Wang L, Chen H, Hill WG, Robson SC, Zeidel ML, Yu W. Targetable purinergic receptors P2Y12 and A2b antagonistically regulate bladder function. JCI Insight 2019. PubMed
  • Takenaka MC, Gabriely G, Rothhammer V, Mascanfroni ID, Wheeler MA, Chao CC, Gutiérrez-Vázquez C, Kenison J, Tjon EC, Barroso A, Vandeventer T, de Lima KA, Rothweiler S, Mayo L, Ghannam S, Zandee S, Healy L, Sherr D, Farez MF, Pratt A, Antel J, Reardon DA, Zhang H, Robson SC, Getz G, Weiner HL, Quintana FJ. Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nat Neurosci 2019. PubMed
  • Zhu C, Wu L, Lv Y, Guan J, Bai X, Lin J, Liu T, Yang X, Robson SC, Sang X, Xue C, Zhao H. The fusion landscape of hepatocellular carcinoma. Mol Oncol 2019. PubMed
  • Wiltberger G, Wu Y, Lange U, Hau HM, Tapper E, Krenzien F, Atanasov G, Benzing C, Feldbrügge L, Csizmadia E, Broschewitz J, Bartels M, Seehofer D, Jonas S, Berg T, Hessel P, Ascherl R, Neumann UP, Pratschke J, Robson SC, Schmelzle M. Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis. Aliment Pharmacol Ther 2019; 49:779-788. PubMed
  • Zhang H, Vijayan D, Li XY, Robson SC, Geetha N, Teng MWL, Smyth MJ. The role of NK cells and CD39 in the immunological control of tumor metastases. Oncoimmunology 2019; 8:e1593809. PubMed
  • Hirata Y, Kakiuchi M, Robson SC, Fujisaki J. CD150high CD4 T cells and CD150high Tregs regulate hematopoietic stem cell quiescence via CD73. Haematologica 2018. PubMed
  • Lin J, Long J, Wan X, Chen J, Bai Y, Wang A, Yang X, Wu Y, Robson SC, Sang X, Zhao H. Classification of gallbladder cancer by assessment of CD8 TIL and PD-L1 expression. BMC Cancer 2018; 18:766. PubMed
  • Atanasov G, Dietel C, Feldbrügge L, Benzing C, Krenzien F, Brandl A, Katou S, Schierle K, Robson SC, Splith K, Wiltberger G, Reutzel-Selke A, Jonas S, Pascher A, Bahra M, Pratschke J, Schmelzle M. Angiogenic miRNAs, the angiopoietin axis and related TIE2-expressing monocytes affect outcomes in cholangiocarcinoma. 2018; 9:29921-29933. PubMed
  • 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 2014; 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 2013; 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