A "Google Maps" of the immune system
The innate immune system's action is a double-edged sword in cancer. Although normally it should fight the spread of cancer, it can also play a role in promoting the development of a tumor
explains Inna Kuperstein, researcher in bioinformatics.
In order to get a better idea of what was going on, Inna Kuperstein coordinated the development of a mapped and interactive representation of this system. Conducted in close collaboration with the immunologists of Institut Curie, including Sebastian Amigorena and Vassili Soumelis, this work was published on 22th October in Nature Communications, a prestigious open access journal, meaning that the content is available free of charge. This new tool is made available to all members of the scientific and medical community worldwide, who may use it to better understand its action, but also enhance, improve and customize it according to their needs.
The innate immune system is a complex one, which involves several types of cells such as macrophages, dendritic cells and NK lymphocytes (natural killers). The presence and behavior of these cells are controlled by a plethora of biological factors. The tumors cells are immersed in this microenvironment which can have a critical impact on the progression of the disease and the response to treatments.
This is why the lack of integrated resources describing the complexity of the innate immune system's response to cancer is an obstacle to interpreting high-throughput data
explains Sebastian Amigorena, CNRS director of Institut Curie Immunotherapy center.
This map that links all the elements of the innate immune system therefore offers researchers and physicians a complete and intuitive overview of the phenomena at work.
We can integrate into the map data from patients or experimental models and get an immediate idea of the role that the innate immune system will play in," comments Dr. Vassili Soumelis, Inserm physician-researcher. We can then use the map to help us in prediction of the patient's response to a particular treatment, and choose the best combination of medication and the best therapeutic strategy.
The creation of this map required a huge effort, starting with the exhaustive reading of the entire scientific literature available on this topic
adds Inna Kuperstein. This includes 837 articles read by Maria Kondratova, researcher at Institut Curie and leading author of this publication. She extracted the information concerning over 1,000 biochemical reactions involving 582 proteins and presented them in the form of a map that ended up containing 1,466 "nodes" linked by several thousands of reactions. The molecular processes involved in main biological phenomena are grouped together into the regions representing tumor growth, tumor recognition, recruitment of immune cells, etc.
This map will no doubt be useful for introducing the biological knowledge on the immune system into the analysis of big data in cancer, using artificial intelligence methods
explains Andrei Zinovyev, scientific coordinator of the Cancer systems biology team.
In the article, a concrete example of this approach is described on the study of single-cell sequencing data in melanoma. This analysis, designed by Andrei Zinovyev and performed by Urszula Czerwinska and Nicolas Sompairac, helped to distinguish several sub-types of immune cells with separate functions within a tumor.
It is important that the map resource and the data used to create them are made available on several online platforms.
This tool is not meant to remain static. Researchers can use it to perform more sophisticated analyses, cut or extend the map as needed...
explains Emmanuel Barillot, Inserm director of the Bioinformatics department at Institut Curie, who is impatiently awaiting feedback from the international community on this innovative tool.