For several years now, the development of new immunotherapy techniques has focused on using the body's own antibodies to fight cancer. T-lymphocytes play an important role in this, since they are able to detect and destroy cancer cells. Scientific research has therefore largely concentrated on the activation of T-lymphocytes in immunotherapy. Despite great advances in this field, the current therapies are only permanently effective in less than 50% of patients.
The success of modern immunotherapies essentially depends upon the degree of inflammation in the tumour. Working in collaboration with the European Bioinformatics Institute of the European Molecular Biology Laboratory, a team of researchers led by dermatologist and bioinformatician Johannes Griss and the group led by dermatologist Stephan Wagner from MedUni Vienna's Department of Dermatology has now made an important find: particular subtypes of B-lymphocytes regulate, amongst other things, the recruitment and activation of T-lymphocytes in melanoma. In this way, they are able to support immune responses against melanoma cells, thereby significantly increasing the success of immunotherapies.
"Our results show that the presence of these B-cell subtypes in the tumour tissue even before treatment can predict an effective response and improved survival of melanoma patients receiving immunotherapy," explains the study’s lead author Johannes Griss. Conversely, in the absence of B-lymphocytes, modern immunotherapies are less effective. "We are now able to use this data to identify a group of patients that may especially benefit from immunotherapies. Our results also provide the basis for developing immunotherapeutic approaches that not only conserve these particular B-cell subtypes but can even activate them," adds last author Stephan Wagner.
The project was supported by the Austrian Science Funds (FWF) (P31127-B28), the European Research Council (ERC), the National Institute of Health and the Dr Miriam and Sheldon G. Adelson Medical Research Foundation.
Service: Nature Communications
B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma. Johannes Griss, Wolfgang Bauer, Christine Wagner, Martin Simon, Minyi Chen, Katharina Grabmeier-Pfistershammer3, Margarita Maurer-Granofszky, Florian Roka1, Thomas Penz, Christoph Bock, GaoZhang6, Meenhard Herlyn, Katharina Glatz, Heinz Läubli, Kirsten D. Mertz, Peter Petzelbauer, Thomas Wiesner, Markus Hartl, Winfried F. Pickl, Rajasekharan Somasundaram, Peter Steinberger, Stephan N. Wagner. DOI 10.1038/s41467-019-12160-2