T cells are crucial in the immune protection against invading pathogens, and play a central role in the control of cancer. Efficient immune responses and differentiation of T cells are regulated by the spatio-temporal availability of co-stimulatory and co-inhibitory molecules. Research from our lab and others has demonstrated that co-stimulation acts in a collaborative manner to induce efficacious T cell responses, as exemplified by the collaboration between members of the TNFR superfamily (e.g. CD27/CD70, OX40/OX40L) and CD28 family (CD28/CTLA-4, PD-1/PDL-1). Inhibition or dysregulation of co-stimulation constitutes an important mechanism of tumor immune evasion, while therapeutic targeting of co-stimulatory and co-inhibitory receptors can induce effective anti-tumor responses in the clinic, as evidenced by immune checkpoint blockade therapy. However, the timing and nature of co-stimulatory signals regulating the recruitment and functionality of T cells in infectious and malignant disease remains incompletely understood.
Our research focusses on the cellular and molecular mechanisms that integrate co-stimulatory and co-inhibitory signals to instruct efficient T cell responses. Using innovative technologies, including epigenetic, transcriptional and proteomic profiling, we aim to dissect the co-stimulatory pathways regulating effective T cell activation and differentiation, and employ this knowledge to rationally improve cancer immunotherapy.
I obtained my Bachelor and Master of Science degree in Molecular Biotechnology at the Technical University of Munich (TUM), during which I performed a research internship at the Walter & Eliza Hall Institute of Medical Research (WEHI) in Melbourne, investigating the role of transcription factors in the formation of tissue-resident memory T (TRM) cells. With the completion of my Master studies, I moved to the Netherlands to start my PhD research on the transcriptional regulation and secondary responses of tissue-resident T cells under the supervision of Klaas van Gisbergen and René van Lier at Sanquin Research and the Amsterdam University Medical Centre. After graduating cum laude in the fall of 2020, I started my Postdoctoral research in the lab of Ramon Arens at the Department of Immunology of the LUMC to study the regulation of T cell responses through co-stimulatory pathways.
Tissue-resident memory CD8+ T cells shape local and systemic secondary T cell responses
Behr FM, Parga-Vidal L, Kragten NAM, van Dam TJP, Wesselink TH, Sheridan BS, Arens R, van Lier RAW, Stark R, van Gisbergen KPJM.
Nat. Immunol. 21, 1070-1081 (2020). doi.org/10.1038/s41590-020-0723-4
Circulating memory CD8+ T cells are limited in forming CD103+ tissue‐resident memory T cells at mucosal sites after reinfection
Behr FM, Beumer‐Chuwonpad A, Kragten NAM, Wesselink TH, Stark R, van Gisbergen KPJM.
Eur. J. Immunol. (2020). doi.org/10.1002/eji.202048737
TRM maintenance is regulated by tissue damage via P2RX7
Stark R, Behr FM, Wesselink TH, Kragten NAM, Arens R, Koch-Nolte F, van Gisbergen KPJM, van Lier RAW.
Sci. Immunol. 3, eaau1022 (2018). doi.org/10.1126/sciimmunol.aau1022