Anti-tumour immune responses

In recent years, it has become apparent that our immune system can control the outgrowth of cancer. A fundamental question that stems from this observation has been how the human immune system can distinguish cancer cells from healthy body cells and how an improved understanding of the tumour microenvironment, in particular the interaction between the tumour and the host’s immune system, can be used for diagnostic purposes.

The tumour microenvironment is complex, comprising, together with tumour cells and vascular vessels, various types of infiltrating immune cells. Jérôme Galon showed that the location, density, and type of the different immune cell populations within a tumour (defined as the “immune contexture”) indicate the disease prognosis and the efficacy of various cancer therapies. He has shown for the first time in humans that the evolution of tumor clones is dependent on the recognition of neoantigens by T lymphocytes. He initiated and coordinated the largest worldwide multicentre consortium trialling a method, known as the “Immunoscore”, to estimate the prognosis of cancer patients based on the immune contexture and the cytotoxic T-cells. The results of the study demonstrated that the Immunoscore has a greater prognostic value than the classical cancer staging system, providing important information for the personalised management of cancer patients. As a result, the Immunoscore was introduced into the World Health Organization (WHO) book for Digestive System Tumours classification, as well as the Clinical Practice Guidelines for gastrointestinal cancer, in 2020.

Ton Schumacher uses a technology-based approach to analyse immune function. Through development of novel assay systems, his research group has made it possible to describe with unprecedented depth which antigens are seen by the T cells that infiltrate human tumours. Schumacher and co-workers subsequently used these technologies to demonstrate that T cells in human cancers, such as melanoma and lung cancer, frequently respond to newly formed antigens (“neoantigens”) that arise as a consequence of DNA mutations. His research provided the first evidence that immune checkpoint blockade, the most widely used form of cancer immunotherapy, can increase the capacity of the T cell-based immune system to recognize such neoantigens. Finally, the observation by Schumacher and others that T cell-based cancer immunotherapies show the most profound activity in cancer types with large amounts of DNA damage provides independent evidence for the role of cancer neoantigens in human tumour control and has inspired the development of neoantigen-directed cancer therapies.

Ton Schumacher and Jérôme Galon have opened a new view of cancer, in which the role of the patient’s immunity is better appreciated and characterised. Together, their research provides patients with improved cancer diagnosis and novel opportunities for therapeutic intervention.

Prof. Ton Schumacher

The Netherlands Cancer Institute
Plesmanlaan 121
1066 CX Amsterdam
The Netherlands

Tel: +31 20 512 2072
t.schumacher@nki.nl
www.nki.nl/research/research-groups/ton-schumacher/