Immune Modulation in Cancer
Dr. Martina Seiffert
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Dr. Martina Seiffert
Team Leader
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Tel.: 06221 42-4586
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My group is interested in tumor immunology and the microenvironment in non-Hodgkin B-cell lymphoma and brain metastasis of breast and lung cancer, with a focus on cancer-induced immune suppression and inflammation as a driver of disease. We aim at identifying mediators and molecular mechanisms of crosstalk between the cancer cells and their surrounding neighbourhood, whereby we concentrate on immune cells of the myeloid and lymphoid lineages. We use our findings to develop and test novel immunotherapy approaches in patient-derived coculture and genetic mouse models.
Schematic presentation of the approaches we use to decipher the heterogeneity and pathological relevance of the tumor microenvironment in B-cell lymphoma and brain metastasis of breast and lung cancer.
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The complex cellular and molecular composition of tumors is essential for their pathobiology. In the past, we were able to identify molecular mechanisms and candidate molecules that are responsible for cancer-induced remodeling of the microenvironment and the immune system.
Our current work focusses on an in-depth characterization of immune and stromal cells in B-cell lymphoma and brain metastases, with the goal to identify novel mechanisms of tumor support and immune escape, and to suggest candidate genes and pathways for the development of novel therapy approaches. This includes also the identification of prognostic or predictive markers and unravelling mechanisms of treatment resistance. We are specifically interested in cancer-associated T-cell exhaustion, in myeloid-derived suppressor cell function, and in mediators that are responsible for both of these phenotypes, including secreted factors and vesicles.
We use single-cell transcriptome and flow cytometry analyses of primary tumor tissue and blood, spatial analyses including multiplex tissue staining and in-situ transcript quantification, ATAC-seq and chromatin immunoprecipitation followed by DNA-sequencing to decipher transcription factor regulatory networks, proteome analyses, as well as functional and treatment studies in vitro and in mouse models to validate the relevance of identified candidate genes and pathways.
To this end, we cooperate with academic and industrial partners and are in close contact with our colleagues in the clinic.
Selected Publications
- Bola S.Hanna, Laura Llaó-Cid, Murat Iskar, Philipp M.Roessner,Lara C.Klett, John K.L.Wong, Yashna Paul, Nikolaos Ioannou, Selcen Öztürk, Norman Mack, Verena Kalter, Dolors Colomer, ElíasCampo, Johannes Bloehdorn, Stephan Stilgenbauer, Sascha Dietrich, Manfred Schmidt, Richard Gabriel, ..., MartinaSeiffert, Science Direct, Interleukin-10 receptor signaling promotes the maintenance of a PD-1int TCF-1+ CD8+ T cell population that sustains anti-tumor immunity
- Roessner PM*, Llaó Cid L*, Lupar E*, Roider T, Bordas M, Schifflers C, Arseni L, Gaupel AC, Kilpert F, Krötschel M, Arnold SJ, Sellner L, Colomer D, Stilgenbauer S, Dietrich S, Lichter P, Izcue A*, Seiffert M*. EOMES and IL-10 regulate anti-tumor activity of T regulatory type 1 CD4+ T-cells in chronic lymphocytic leukemia. Leukemia, 35(8): 2311-2324, 2021. *shared authorship.