My group works on different aspects of tumor immunology in malignant melanoma with a special emphasis on translational research. Melanoma is a highly mutated and immunogenic malignancy that can be treated with both immunotherapy and targeted agents. However, a substantial number of patients with metastatic disease has no, minimal or short-lived benefit from these therapeutics.
In my group, we are trying to understand which patients are most likely to benefit from immunotherapy. In particular, we want to understand which antigens on cancer cells can be detected by human T cells. So-called (mutated) neoantigens seem to play a major role in this perspective. These tumor antigens are formed by somatic mutations and thereby are private. Recently, we identified another class of neoantigens. These antigens (TURCs) are tumor-specific, recurrent and of cryptic origin since they cannot be attributed to known proteins. We were able to show that TURCs are much more frequent than mutated neoantigens. Currently, we are trying to validate TURCs as T cell antigens and to understand the mechanisms of their formation. Our long-term goal is to develop personalized immunotherapies based on our findings.
Targeted therapy of advanced melanoma is already personalized. In patients with BRAFV600 (~50% of all melanomas), dual MAPK inhibition can prolong survival. However, the majority tumors eventually become resistant and progress. To overcome resistance, combination of targeted therapies and immunotherapy has been proposed. To this end, we are exploring the immunological aspects and consequences of targeted therapy in melanoma patients and how oncogenes modulate the interaction of malignant cells with the immune system. We were able to show that different targeted drugs used against BRAFV600 mutant melanoma have a specific impact on the human immune system. Currently, we are investigating how myeloid cells influence the efficacy of MAPK inhibition in melanoma. Ultimately, we want to understand how to combine or sequence targeted therapy and immunotherapy for maximal patient benefit.
Most important publications
Erhard F, Dölken L, Schilling B, Schlosser A. (2020) Identification of the cryptic HLA-I immunopeptidome. Cancer Immunol Res, accepted for publication
Liu D**, Schilling B**, Liu D, Sucker A, Livingstone E, Zimmer L, Gutzmer R, Satzger I, Loquai C, Grabbe S, Vokes N, Margolis C, He MX, Elmarkaby H, Dietlein F, Tracy A, Gogas H, Goldinger SM, Utikal J, Blank CU, Rauschenberger R, von Bubnoff D, Krackhardt A, Weide B, Haferkamp S, Kiecker F, Garraway L, Regev A, Flaherty K, Paschen A, van Allen EM*, Schadendorf D*. (2019) Integrative molecular and clinical modeling of clinical outcomes to PD-1 blockade in metastatic melanoma patients. Nat Med. Dec;25(12):1916-1927. **equally contributing first authors, *corresponding authors
Van Allen EM**, Miao D**, Schilling B**, Shukla SA, Blank C, Zimmer L, Sucker A, Hillen U, Geukes Foppen MH, Goldinger SM, Utikal J, Hassel JC, Weide B, Kaehler KC, Loquai C, Mohr P, Gutzmer R, Dummer R, Gabriel S, Wu CJ, Schadendorf D*, Garraway LA*: Genomic correlates of response to CTLA4 blockade in metastatic melanoma. Science 350(6257):207-11 (2015). **equally contributing first authors, *corresponding authors
Schilling B**, Sondermann W, Zhao F, Griewank K, Livingstone E, Sucker A, Zelba H, Weide B, Trefzer U, Wilhelm T, Loquai C, Berking C, Hassel J, Kähler KC, Utikal J, Al Ghazal P, Gutzmer R, Goldinger SM, Zimmer L, Paschen A, Hillen U*, Schadendorf D*: Differential influence of vemurafenib and dabrafenib on patients’ lymphocytes despite similar clinical efficacy in melanoma. Ann Oncol 25(3):747-53 (2014). **corresponding author, *equally contributing senior authors
Schilling B**, Sucker A, Griewank K, Zhao F, Weide B, Görgens A, Giebel B, Schadendorf D, Paschen A: Vemurafenib reverses immunosuppression by myeloid-derived suppressor cells. Int J Cancer 133(7):1653-63, (2013). **corresponding author