Cancérogenèse : Surexpression de TRF2, marqué en vert, dans les vaisseaux tumoraux, marquage rouge, dans un cancer ovarien. ©Inserm/Wagner, Nicole, 2014

As tumors develop, they evolve genetically. How does the immune system act when faced with tumor 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 on November 23, 2018.

Over time, the uncontrolled proliferation of tumor cells results in the accumulation of new mutations and changes to their genome. This gradual process creates significant genetic diversity among the cancer cells in any given patient. And although the cells in the immune system, especially T cells, are potentially able to eliminate these abnormal cells, tumor diversity can have a harmful effect, complicating the action of the immune system and rendering some therapies ineffective. Understanding this frantic race between tumor development and the immune response is key to the success of future immunotherapy techniques.

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 tumors influence this tumor heterogeneity. They demonstrated that the immune system can employ mechanisms to significantly reduce tumor diversity, favoring the emergence of more genetically homogeneous tumor cells.

In their study, the scientists marked each cancer cell subclone with a separate color in a mouse model. By monitoring these different 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.

Visualizing the action of stained immune cells.
In this video, the tumor cells are shown in gray. The tumor-specific T-cells, in purple, come into contact with the cancer cells and destroy them. The killed cells are shown in blue. In green, the control cells circulate but do not kill the tumor cells. © Institut Pasteur / Philippe Bousso

Visualizing different clusters of cancer cell clones.
This video illustrates how tumor subclones, each marked by a different color (blue, orange and green), develop in the bone marrow. The vessels are shown in white. © Institut Pasteur / Philippe Bousso

The same impact on the heterogeneity of tumor 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.

This research shows that taking into account the interaction between immunotherapies and tumor heterogeneity could contribute to the development of optimum therapeutic combinations and sequences.

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).

These contents could be interesting :

A valve made from human collagen opens up new avenues for the treatment of a paediatric heart disease

Researchers from Inserm have developed a pulmonary valve using human collagen. A device that could ultimately be a game-changer in the treatment of paediatric heart diseases, such as tetralogy....

Dengue and Zika Viruses: Towards a Better Understanding of the Mechanisms of Transmission

Aedes mosquitoes are the principal vectors of dengue and other arboviruses, including Zika, for which no vaccines or antiviral treatments currently exist. Understanding the factors that influence the transmission....