What we investigate
Our laboratory has a long-standing interest in the communication networks, which control and drive tissue inflammation. These communication conduits studied in models of skin inflammation are harnessed in immunotherapy of patients suffering from skin cancer. We aim to understand the intricate interactions between immune cells and the affected tissue and to define new therapeutic targets for intervention.
KEYWORDS
inflammation, cancer, cytokines, single-cell cytometry, immunophenotyping
Our research in more detail
Treatment of aggressive skin cancers made a quantum leap with the advent of immunotherapy that inhibits endogenous T cell inhibitions (check-points). Unfortunately, only 50% of patients show a durable clinical benefit and predictive biomarkers of clinical response are urgently needed. To interrogate the immune compartment of cancer patients we have developed the capacity to interrogate a large number of patients through high-dimensional single cell mapping of routine biopsy material. The main idea is to interrogate the systemic immune compartment as well as the local tumor microenvironment (TME) to identify predictive biomarkers for treatment response. Moreover, understanding the complex immune network required for (or preventing) a successful and sustainable anti-tumor immune response, will be possible through in depth quantitative immunophenotyping of the large cohort of patients in Zurich. This discovery pipeline can be expanded to studying the immunophenotype of other skin cancer entities as well as other therapies (i.e., combination immunotherapy, oncolytic viruses, and targeted therapy). This high-throughput systematic approach will provide a rich and in depth view of the TME in skin cancer and thereby help to improve therapeutic targeting.
Selected publications
SKINTEGRITY.CH Principal Investigators are in bold:
- de Melo BMS, Veras FP, Zwicky P, Lima D, Ingelfinger F, Varela T, da Silva Prado D, Schärli S, Publio G, Hiroki CH, Melo PH, Saraiva A, Norbiato T, Lima L, Ryffel B, Vogl T, Roth J, Waisman A, Nakaya HI, da Silva Souza C, Cunha FQ, Cunha TM, Becher B, Alves-Filho JC. (2023) S100A9 drives the chronification of psoriasiform inflammation by inducing IL-23/type 3 immunity. J Invest Dermatol. In press doi: 10.1016/j.jid.2023.02.026
- Nuñez NG, Berner F, Friebel E, Unger S, Wyss N, Gomez JM, Purde MT, Niederer R, Porsch M, Lichtensteiger C, Kramer R, Erdmann M, Schmitt C, Heinzerling L, Abdou MT, Karbach J, Schadendorf D, Zimmer L, Ugurel S, Klümper N, Hölzel M, Power L, Kreutmair S, Capone M, Madonna G, Cevhertas L, Heider A, Amaral T, Hasan Ali O, Bomze D, Dimitriou F, Diem S, Ascierto PA, Dummer R, Jäger E, Driessen C, Levesque MP, van de Veen W, Joerger M, Früh M, Becher B, Flatz L. (2022) Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors. Med, 4(2), 113-129. doi: 10.1016/j.medj.2022.12.007.
- Ingelfinger F, Gerdes LA, Kavaka V, Krishnarajah S, Friebel E, Galli E, Zwicky P, Furrer R, Peukert C, Dutertre CA, Eglseer KM, Ginhoux F, Flierl-Hecht A, Kümpfel T, De Feo D, Schreiner B, Mundt S, Kerschensteiner M, Hohlfeld R, Beltrán E, Becher B. (2022) Twin study reveals non-heritable immune perturbations in multiple sclerosis. Nature. 603(7899), 152-158. doi: 10.1038/s41586-022-04419-4.
- Zwicky P, Ingelfinger F, Silva de Melo BM, Ruchti F, Schärli S, Puertas N, Lutz M, Phan TS, Kündig TM, Levesque MP, Maul JT, Schlapbach C, LeibundGut-Landmann S, Mundt S, Becher B. (2021) IL-12 regulates type 3 immunity through interfollicular keratinocytes in psoriasiform inflammation. Sci Immunol. 6(64), eabg9012. doi: 10.1126/sciimmunol.abg9012.
- Tuzlak S, Dejean AS, Iannacone M, Quintana FJ, Waisman A, Ginhoux F, Korn T, Becher B. (2021) Repositioning TH cell polarization from single cytokines to complex help. Nat Immunol. 22(10), 1210-1217. doi: 10.1038/s41590-021-01009-w.