Our research focuses on leveraging the immune system to combat cancer, with a special emphasis on translating findings into clinical trials and ultimately therapies.
Cellular therapies for cancer:
Our team's extensive work has centered on understanding B cell receptor (BCR) biology and the downstream signaling pathways in blood cancers and immunological disorders. The importance of this axis is underscored by successful therapeutics targeting its signaling mediators. We're particularly interested in disease-specific BCR configurations enriched in various contexts, which can drive tumor growth or autoreactivity. We plan to use this knowledge to develop innovative immunotherapies like chimeric antigen receptor (CAR) T cells, aiming to target disease-causing clones directly. Our approach seeks to mitigate issues faced by current therapies and provide better clinical outcomes.
Predicting Immune Checkpoint Blockade Response:
Although Immune Checkpoint Blockade (ICB) has transformed cancer treatment, less than half of patients respond effectively. We're focused on identifying response predictors, especially in colorectal, gastric, and head and neck cancers. Our research revealed that combining PD-L1 targeting with chemotherapy selects for PD-L1 escape mutations in certain patients with high-affinity Fcγ receptor 3a (FcγR3a) variants, enhancing their response. In HER2 positive esophagogastric adenocarcinoma, we identified liquid biomarkers predicting treatment efficacy of chemotherapy-free regimens. These insights aid in tailoring treatments for improved patient outcomes.
Understanding Lymphocyte Behavior:
Lymphocytes are critical for health but can cause harm through malignancy or autoimmunity. Our study delves into how recurrent mutations in lymphomas transform antigen receptor signals into proliferation or prevent self-antigen-induced clonal deletion. Hereditary monogenetic autoinflammatory diseases serve as models, illuminating the propagation of autoreactive cells and early lymphomagenesis.
Long-Term Effects of Viral Infections:
Viral infections can lead to long-term health complications. We're investigating post-SARS-CoV-2 and hepatitis C virus (HCV) infection outcomes. Our research on COVID-19 patients revealed TCR and BCR signatures linked to immune responses and autoimmunity. Long-term effects seem rooted in persistent hyperinflammatory cytokine signaling. For HCV, we discovered BCR repertoire imprints that persist after therapy, potentially contributing to lymphomagenesis. Our findings provide insights into the mechanisms behind lingering post-infection effects.
In summary, our research spans a broad spectrum from lymphocyte biology to anti-tumor immune responses and cellular therapies. By translating discoveries into practical applications, we aim to advance the field of immuno-oncology and improve patient outcomes.
For more information please visit our Lab website.
Fig.1: T cell repertoire analysis and phenotyping in COVID-19 patients. (A) TRBV metrics and principal component analysis (PCA) of TRBV-J usage in patients with active COVID-19 or after recovery as compared to healthy controls (HD). (B) Selected differentiation and maturation profiles of peripheral T cells. (C) PCA of normalized clonotype frequency patterns over time (left) and trajectories of pattern 1 (expanding) and pattern 2 (contracting). From Schultheiß et al 2020, Immunity.