Research interests of Prof. Dr. med. et phil. nat. Christoph Schlapbach
Human human interleukin 9-producing T helper memory cells and their role in anti-tumor immune response in malignant skin disease
Human T helper (TH) cells are crucial mediators of the adaptive immune system. To respond to the myriad of infectious and non-infectious challenges, they have evolved into distinct subsets such as TH1, TH2, or TH17 cells. IL-9 producing TH9 cells have recently been proposed as a novel subset of TH cells and studies in animal models suggest a protective role for these cells in tumor immunity. However, studies of TH9 cells thus far have largely been limited to TH cells differentiated in vitro. Studies of human in vivo differentiated TH9 cells are lacking. Therefore, the existence of TH9 cells as an authentic cell type has been called into question.
Our data now indicate for the first time the existence of human in vivo differentiated TH9 cells, thus raising the possibility to investigate their true identity and functional properties. In addition, we find large numbers IL-9 expressing cells in the immune infiltrate of human melanoma, thus warranting further investigation of the role of TH9 cells in the human anti-melanoma immune response.
The overarching aim of our research is to investigate the identity and properties of human TH9 cells and their role in the anti-melanoma immune response. Based on our preliminary data, we hypothesize that TH9 cells are in fact a distinct subset and that they can be identified by a specific set of skin-homing receptors. Because of the robust tumor immunity mediated by TH9 cells in mice, we hypothesize that they can be found at higher numbers in the immune infiltrate of primary melanomas compared to metastasized melanoma, since metastasis requires immune evasion of the tumor, and that the number of TH9 cells correlates with disease prognosis.
Established immunological methods for the analysis of human T cell biology (cell culture, intracellular FACS staining, FACS sorting, ELISA, Luminex cytokine multiplex assay, RT-PCR, immunohistochemistry, immunofluorescence double staining) are used in combination with a novel method for ex vivo analysis of human tissue-resident T cells.
Answering the questions raised in this project will increase our understanding of TH cell biology, lead to a thorough characterization of human TH9 cells and shed light on their contribution to the anti-melanoma immune response. Based on surprising recent findings that TH9 cells mediate superior tumor immunity in mice, it seems highly promising to investigate the biology of TH9 cells in humans; a better understanding of these cells may lead to the development of innovative T cell based immunotherapies for malignant melanoma.
Students in life sciences with an interest in performing a master thesis or MD thesis in human T cell biology/tumor immunology may contact C. Schlapbach directly via email.
Selected Publications – Original articles
1. M. Kakeda, M. Arock, C. Schlapbach, N. Yawalkar
Increased expression of heat shock protein 90 in keratinocytes and mast cells in psoriasis
Journal of the American Academy of Dermatology, in press
2. C. Schlapbach, C. Yang, R. Watanabe, A. Gehad, E. Guenova, J. Teague, N. Yawalkar, T.S. Kupper, R.A. Clark
Human TH9 cells are skin-tropic and have autocrine and paracrine pro-inflammatory capacity
Science translational medicine, 2014
3. A.L. Gerber, A. Münst, C. Schlapbach, M. Shafighi, D. Kiermeir, R. Hüsler, R.E. Hunger
High expression of FoxP3 in primary melanoma is associated with tumor progression
British Journal of Dermatology, 2013.
4. E. Guenova, R. Watanabe, J. Desimone, J. Teague, Y. Jiang, M. Dowlatshahi, A. Gehad, C. Schlapbach, K. Schaekel, A. Rook, M. Tawa, D. Fisher, T. Kupper, R. Clark
Th2 cytokines from malignant cells suppress Th1 responses and enforce a global Th2 bias in leukemic cutaneous T cell lymphoma
Clinical Cancer Research, 2013.
5. Purwar, R., C. Schlapbach, S. Xiao, H.S. Kang, W. Elyaman, X. Jiang, A.M. Jetten, S.J. Khoury, R.C. Fuhlbrigge, V.K. Kuchroo, R.A. Clark, T.S. Kupper
Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells
Nature medicine, 2012.
6. Clark, R.A., R. Watanabe, J.E. Teague, C. Schlapbach, M.C. Tawa, N. Adams, A.A. Dorosario, K.S. Chaney, C.S. Cutler, N.R. Leboeuf, J.B. Carter, D.C. Fisher, T.S. Kupper
Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients.
Science translational medicine, 2012.
7. C. Schlapbach, Zawodniak, A., Irla, N., Adam, J., Hunger, R.E., Yerly, D., Pichler, W.J., and Yawalkar, N.
NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions.
8. C. Schlapbach, Hanni, T., Yawalkar, N., and Hunger, R.E.
Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa.
Journal of the American Academy of Dermatology, 2011.
9. C. Schlapbach, Yerly, D., Daubner, B., Yawalkar, N., and Hunger, R.E.
Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma.
Journal of Dermatological Science, 2011.
10. C. Schlapbach, Ochsenbein, A., Kaelin, U., Hassan, A.S., Hunger, R.E., and Yawalkar, N.
High numbers of DC-SIGN+ dendritic cells in lesional skin of cutaneous T-cell lymphoma.
Journal of the American Academy of Dermatology, 2010.
11. C. Schlapbach, Yawalkar, N., and Hunger, R.E.
Human beta-defensin-2 and psoriasin are overexpressed in lesions of acne inversa.
Journal of the American Academy of Dermatology, 2009.