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Tertiary lymphoid structures in metastatic melanoma and non-small cell lung cancer tissues as predictive markers for the outcome of checkpoint inhibitor treatment

Principal Investigators

Maries van den Broek , Institute of Experimental Immunology, University of Zurich
Lukas Flatz, Departments of Oncology and Dermatology, Kantonsspital St.Gallen, SNSF Professor, University of Zurich

Fellow

Oltin T. Pop, MD, PhD

Keywords

TERTIARY LYMPHOID STRUCTURES, IMMUNE CHECKPOINT INHIBITORS, BIOMARKERS

Summary

Treatment with immune checkpoint inhibitors revolutionized the treatment of many stage IV cancers including melanoma and non-small cell lung cancer (NSCLC). Such therapies result in clinical benefit in only a proportion of patients and often induce toxicities. Predicting benefit and adverse side effects, however, is currently not possible due to the lack of biomarkers. Cancer-associated tertiary lymphoid structures (TLS) correlate with prolonged survival, presumably because they act as a local hub that supports tumor-specific immunity. TLS can be readily quantified in H&E sections, which allows the integration of this parameter in the standard pathology workflow. We will investigate whether the presence of TLS within the tumor microenvironment correlates with the clinical response and/or development of toxicities in patients treated with immune checkpoint inhibitors. We will use two independent prospective cohorts of patients with melanoma and NSCLC. In addition, we will screen whether conventional laboratory parameters including blood sedimentation rate, white blood count and inflammation markers can be used as a surrogate marker of TLS, clinical response or adverse effects in the blood. Our findings will help us defining a signature that predicts clinical response as well as adverse effects to immune checkpoint inhibition that can be integrated into routine pathology.