Janine Kemming

Project title: Immunological mechanisms behind rheumatological adverse events induced by immune checkpoint inhibitors

Host Institution: Technical University of Denmark (DTU)

Host Supervisor: Prof. Sine Hadrup

Co-host Institution: Technical University of Munich (TUM)

Co-host Supervisor: Prof. Dirk Busch

Summary project: Autoimmune diseases like inflammatory arthritis (IA) significantly impact the quality of life for many patients. The mechanisms of disease development, however, are poorly understood, hence challenging the design of precise therapeutic strategies.
Recently, a new group of patients is emerging, namely those that develop IA as a consequence of immunotherapy for cancer. Immune checkpoint inhibition (ICI) releases the breaks of the immune systems which in term can lead to induction of autoimmune diseases, among them IA. While we aim to find strategies to reduce autoimmune reactivity during ICI, this has provided us with a unique window of opportunity to investigate the mechanisms of the development of autoimmune diseases.
As ICI primarily regulates T-cell reactivity, in this project we will focus on identifying the role of T-cell recognition in the induction of IA during ICI. By sampling PBMC and synovial fluid from patients before, during and after ICI for melanoma, close clinical monitoring for IA initiation and progress together with in-depth T-cell analyses and assessment of T-cell receptor (TCR) affinities in auto-reactive versus cancer-reactive T cells, we aim to detect preconditions in the T-cell department that are associated with autoimmune disease development in this cohort.
Furthermore, we will determine key cellular and molecular mechanisms that underly autoimmune disease (here IA) development, and identify the immune signature related to patients at risk of developing IA during ICI treatment. Such signature can be applied as a biomarker for autoimmune diseases development and patient stratification to different treatment options, depending on the individual risk.