Forschungsprojekt Onkologie

Forschungsgruppe Prof. Alfred Zippelius
Dissecting tumour heterogeneity in lung cancer patiens with an advanced imaging platform

Cancer immunotherapy is nowadays considered the most important advance in the field of oncology following outstanding clinical successes with blockade of immune checkpoints on T cells by monoclonal antibodies (mAbs). These mAbs exhibit remarkable clinical efficacy and are now FDA approved for the treatment of a broad range of tumour types. mAbs work by harnessing the anti-tumour response of patients’ own immune system, in particular CD8+ T lymphocytes. The clinical activity of mAbs is classically reflected by prolongation of survival, but particularly by durable clinical benefits which provoke oncologists to begin to envision immunotherapy as a potentially curative therapeutic manoeuvre. Importantly, therapeutic benefits are currently limited to a minority of treated patients and many patients are resistant to the treatment. Work carried out in our lab aims to understand what are the underlaying reasons for resistance to immunotherapy and how these may be overcome to improve the success rates of cancer patients’ survival.

Tumour niche is often occupied by a variety of immune cells, including T cells, B cells, dendritic cells, macrophages, natural killer cells and neutrophils. Many of these cells are inhibited from performing their function by multiple factors present within the tumour, such as engagement of inhibitory receptors, presence of immunosuppressive cytokines, and cell populations, as well as metabolic factors. Currently we are working on detailed characterization of tumour microenvironment in clinically relevant context of responsiveness to anti-PD-1 therapy with advanced imagining platform called Codex. Codex technology (for CO-Detection by indEXing) was developed at Stanford University in the laboratory of Prof. Garry Nolan. It enables to acquire images of up to 60 antibodies from a single tissue slide, therefore providing enormous insight into cellular complexity and tissue organisation. Image acquisition is followed by complex bioinformatic analysis, which quantifies received signals and provides information on the patterns of cell to cell interactions. Thanks to funding provided by FAG, we were able to arrange a scientific visit to the laboratory of Prof. Garry Nolan in Stanford and gain first-hand experience with Codex imaging. During our stay we have established close collaboration with researchers who developed Codex and this has tremendously strengthened our understanding of the technology, helped to develop experimental protocols and provided us with strong professional support for further research.

We are very excited to be introducing Codex to the Department of Biomedicine at the University Hospital Basel and University of Basel. We will use Codex to visualise different immune cell types within the tumour environment of the lung cancer patients. We will compare the cellular profiles in tumour tissues from patients who respond to immunotherapy to the tissues from the non- responding patients. We aim to identify the cellular interactions which are altered between the two groups, which will provide the springboard for further detailed studies on overcoming resistance to the treatment. Our goal is to advance the field of oncology and ultimately, we aim to provide new avenues for treatment of those patients, who currently cannot be successfully treated with checkpoint inhibitors.

Prof. Alfred Zippelius, Dr. Marta Trüb, Dr. Gianni Monaco