Cytotoxic T cells (CTL) are essential cellular components in the immune response against viruses and cancer. This is why it is essential to better understand the function of these cells and in particular to better understand how these cells manage to kill their target cells or why they fail to do so. Well-known cytotoxic mechanisms consist of forming privileged contacts with target cells, named immunological synapses, in which CTL discharge soluble molecules that perforate the membrane of the target cell and allow the penetration of toxic molecules that kill the target cell. This study reveals a new complementary mechanism by which CTL can kill their targets. The results show that, in addition to the release of soluble molecules, CTL can release particles that contain packaged perforating and toxic molecules protected by a adhesive glycosylated protein shell. These particles, once released, can autonomously kill the target cells, they thus serve as bomb like structures released by the CTL to kill their targets remotely. A better understanding of this newly described mechanism of release of cytotoxic molecules could be useful in developing new strategies to enhance CTL activity against virus infected cells or cancer cells.

Strategies of tumor immunotherapy based on the transfer of CTL specific of tumor antigens, such as CAR-T cells, are very promising. Nevertheless, these therapies are laborious and costly and are, in some cases, limited by the inefficient entry of CAR-T cells within the tumor. The supramolecular attack particles described in this study could potentially be modified to be directed against tumors in simpler and less expensive therapeutic approaches than autologous patient cell transfer.

This study is part of a broader international collaboration with several research groups based in UK, Germany and Italy. We hope that this publication will strengthen the ongoing collaboration and lead to new and more important results.

Discover the article published :

Science. 2020 May 7.
Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells.
Balint Š, Müller S, Fischer R, Kessler BM, Harkiolaki M, Valitutti S, Dustin ML.

This study is coordinated by Professor M. Dustin’s group at the Kennedy Institute of Rheumatology at the University of Oxford, who discovered and described the structure and composition of supramolecular attack particles (SMAPs).
The INSERM team collaborated in this study because of its experience in the field of human cytotoxic T cells and immunological synapses.

key words :

• cytotoxic T cells
  cytotoxicity
  immunological synapse
  immunosurveillance

Contact :

Salvatore Valitutti
Team 20 CRCT

Mail : salvatore.valitutti@inserm.fr

One picture :

A CTL not activated by the target cell (left) or activated (right) is shown. The activated CTL releases supramolecular attack particles (Smaps) that bind to the target cell.