As tumours develop, they evolve genetically. How does the immune system act when faced with tumour cells? How does it exert pressure on the genetic diversity of cancer cells? Scientists from the Institut Pasteur and Inserm used in vivo video techniques and cell-specific staining to visualize the action of immune cells in response to the proliferation of cancer cells. The findings have been published in the journal Science Immunology.
Scientists in the Dynamics of Immune Responses Unit (Institut Pasteur/Inserm), directed by Philippe Bousso, in collaboration with Ludovic Deriano, Head of the Genome Integrity, Immunity and Cancer Unit (Institut Pasteur), investigated how spontaneous immune responses to tumours influence this tumour heterogeneity. They demonstrated that the immune system can employ mechanisms to significantly reduce tumour diversity, favoring the emergence of more genetically homogeneous tumour cells.
In their study, the scientists marked each cancer cell subclone with a separate color in a mouse model. By monitoring these colors, they were therefore able to characterize the evolution of tumor heterogeneity in time and space. They were also able to observe the contacts between T cells and cancer cells and determine how some tumor cells are destroyed. Their research highlights the drastic impact the immune system can have on tumors by reducing their heterogeneity.
The same impact on the heterogeneity of tumour cells has also been observed in response to immunotherapies that release the brakes on the immune system, an approach which was awarded the Nobel Prize in Physiology or Medicine this year.
In addition to the organizations mentioned above, this research was funded by the Fondation de France, the French National Cancer Institute (INCa) and the European Research Council (ERC).
Paper: Idan Milo et al, The immune system profoundly restricts intratumor genetic heterogeneity, Science Immunology (2018). DOI: 10.1126/sciimmunol.aat1435