Suppression of human T cells by 5'-methylthioadenosine

• Applicants: Dr. Michael Aigner; Professor Dr. Andreas Mackensen
• Subject Area: Hematology, Oncology
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190230491

• Final Report Year: 2019

Final Report Abstract

We were able to elucidate the molecular mechanism of MTA induced T cell inhibiton, identifying p53 as a key molecule. Furthermore, we were able to demonstrate that MTA induces metablic changes in T cells that resemble an un-acticated T cell phenotye, strenghtening the data that MTA inhibits T cell activaction. In addition, we could show that NK cells also were impaired in the presence of MTA, and showed a differing molecular mode of inhibition than T cells.

Publications

• (2013). IFN-gamma-driven intratumoral microenvironment exhibits superior prognostic effect compared with an IFN-alpha-driven microenvironment in patients with colon carcinoma. Am J Pathol Dec; 183(6): 1897-1909
  Grenz S, Naschberger E, Merkel S, Britzen-Laurent N, Schaal U, Konrad A, Aigner M, Rau TT, Hartmann A, Croner RS, Hohenberger W, Stürzl M
  (See online at https://doi.org/10.1016/j.ajpath.2013.08.025)
• (2016). LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells. Cell Metab Nov 8; 24(5): 657-671
  Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, Kastenberger M, Bogdan C, Schleicher U, Mackensen A, Ullrich E, Fichtner-Feigl S, Kesselring R, Mack M, Ritter U, Schmid M, Blank C, Dettmer K, Oefner PJ, Hoffmann P, Walenta S, Geissler EK, Pouyssegur J, Villunger A, Steven A, Seliger B, Schreml S, Haferkamp S, Kohl E, Karrer S, Berneburg M, Herr W, Mueller-Klieser W, Renner K, Kreutz M
  (See online at https://doi.org/10.1016/j.cmet.2016.08.011)
• (2016). Suppressive effects of tumor cell-derived 5'-deoxy-5'-methylthioadenosine on human T cells. Oncoimmunology Aug; 5(8): e1184802
  Henrich FC, Singer K, Poller K, Bernhardt L, Strobl CD, Limm K, Ritter AP, Gottfried E, Volkl S, Jacobs B, Peter K, Mougiakakos D, Dettmer K, Oefner PJ, Bosserhoff AK, Kreutz MP, Aigner M, Mackensen A
  (See online at https://doi.org/10.1080/2162402X.2016.1184802)
• (2018). Clinical-grade generation of peptidestimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts. J Transl Med May 9; 16(1): 124
  Gary R, Aigner M, Moi S, Schaffer S, Gottmann A, Maas S, Zimmermann R, Zingsem J, Strobel J, Mackensen A, Mautner J, Moosmann A, Gerbitz A
  (See online at https://doi.org/10.1186/s12967-018-1498-3)
• (2018). Visualizing Single-Cell Secretion Dynamics with Single-Protein Sensitivity. Nano Lett Jan 10; 18(1): 513-519
  McDonald MP, Gemeinhardt A, Konig K, Piliarik M, Schaffer S, Volkl S, Aigner M, Mackensen A, Sandoghdar V
  (See online at https://doi.org/10.1021/acs.nanolett.7b04494)