Isabel Poschke

Analysis and exploitation of the T-cell immune response against pancreatic cancer

I am interested to study the human immune system and how it is modulated by the presence of cancer. My particular interests are T lymphocytes and their interaction with tumor cells and tumor stroma.

The long term goal of my research is to develop immune based therapies that impact cancer patient survival and quality of life.

Pancreatic cancer currently has dismal prognosis and the window for therapeutic intervention is small. This malignancy is often discovered at a late stage; consequently tumor immune escape and tumor-mediated immunosuppression probably represent a profound obstacle for immunotherapy of pancreatic cancer.

My aim is to better understand how pancreatic cancer is recognized by the immune system and what pathways the tumor exploits to exert immunosuppression.

This knowledge can be utilized to design therapies, most likely involving T cells that have been manipulated in vitro to be better equipped to recognize the tumor and survive in the hostile tumor-microenvironment.

I believe that it is crucial not to limit our investigations to the blood, but focus on immunologically relevant sites such as the tumor and its draining lymph nodes. To achieve this, techniques that allow comprehensive and reliable analysis of immunological subsets and functions in limited amounts of cells will be developed.

Scientific Background

• B.Sc. in Molecular Biotechnology, Technical University of Munich, Germany ·M.Sc. in Molecular Biotechnology, Technical University of Munich, Germany
• PhD studies at Karolinska Institute, Dept. of Oncology-Pathology, Cancer Center Karolinska (Prof. R. Kiessling) - focus on myeloid-derived suppressor cells (MDSC) in melanoma patients, and mechanisms of T cell suppression in breast cancer patients ·
• Post-doctoral research fellow, Karolinska Institute, Dept. of Oncology-Pathology, Cancer Center Karolinska (Prof. R. Kiessling) - focus on immune deviation in breast cancer patients, and development of phase I clinical trial protocols for the treatment of malignant melanoma with DC and T cell based therapies
• Post-doctoral research fellow, Div. of Molecular Oncology of Gastrointestinal Cancers, German Cancer Research Center (DKFZ) (Prof. R. Offringa) – focus on T cell immunology in pancreatic cancer patients; characterization of T cell functionality and reactivity; development of T cell based therapies that can be applied in pancreatic cancer

Publications

• I.Poschke, Y. Mao, L.Adamson, F.Salazar-Onfray, G.Masucci, R.Kiessling. Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines; Cancer Immunology Immunotherapy, 2011; in press
• I.Poschke, J. De Boniface, Y. Mao, R. Kiessling. Tumor-induced changes in the phenotype of blood-derived and tumor-associated T cells of early-stage breast cancer patients; International Journal of Cancer, 2011; in press
• I.Poschke*, J. De Boniface*, Y. Mao, R. Kiessling. Tumor dependent down-regulation of the ζ-chain in T and NK cells is detectable in early breast cancer and correlates with immune cell function; International Journal of Cancer, in press (*contributed equally)
• I. Poschke, D. Mougiakakos, R. Kiessling. 2011 Camouflage and Sabotage – tumor escape from the immune system; Cancer Immunology Immunotherapy, 2011 Aug;60(8):1161-71
• I. Poschke*, D. Mougiakakos*, J. Hansson, G. Masucci, R. Kiessling. 2010. Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and over-express CD80, CD83 and DC-Sign; Cancer Res; 70(11):4335-45 (*contributed equally)
• K. Mimura, T. Ando, I. Poschke, D. Mougiakakos, C. Johansson, J. Ichikawa, R. Okita, M. Nishimura, D. Handke, N. Krug, A. Choudhury, B. Seliger, R. Kiessling. 2010. T cell recognition of HLA-A2 restricted tumor antigens is impaired by the oncogene HER2. Int J Cancer, 128(2):390-401
• I. Poschke*, H. Norell*, J. Charo, W.Z. Wei, C.L. Erskine, M.P. Piechocki, K.L. Knutson, J. Bergh, E. Lidbrink, R. Kiessling. 2010. Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial; J Transl Med. 7;8:53. (*contributed equally)
• Carlsten, M., H. Norell, Y. T. Bryceson, I. Poschke, K. Schedvins, H. G. Ljunggren, R. Kiessling, and K. J. Malmberg. 2009. Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J Immunol 183:4921-4930.
• Johansson, C. C., S. Egyhazi, G. Masucci, H. Harlin, D. Mougiakakos, I. Poschke, B. Nilsson, L. Garberg, R. Tuominen, D. Linden, M. F. Stolt, J. Hansson, and R. Kiessling. 2009. Prognostic significance of tumor iNOS and COX-2 in stage III malignant cutaneous melanoma. Cancer Immunol Immunother 58:1085-1094.
• Kruschinski, A., A. Moosmann, I. Poschke, H. Norell, M. Chmielewski, B. Seliger, R. Kiessling, T. Blankenstein, H. Abken, and J. Charo. 2008. Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas. Proc Natl Acad Sci U S A 105:17481-17486.
• Kiessling, R., A. De Geer, C. Johansson, I. Poschke, C. Triulzi, and S. Vertuani. 2008. Progress in vaccination against cancer-7: report of the meeting in Stockholm, September 10-11, 2007. Cancer Immunol Immunother 57:593-599.
• Harlin, H., M. Hanson, C. C. Johansson, D. Sakurai, I. Poschke, H. Norell, K. J. Malmberg, and R. Kiessling. 2007. The CD16- CD56(bright) NK cell subset is resistant to reactive oxygen species produced by activated granulocytes and has higher antioxidative capacity than the CD16+ CD56(dim) subset. J Immunol 179:4513-4519.