Researchers Reveal in 3D How T-Cells Destroy Tumors

A team from the University of Geneva (UNIGE) and the Vaud University Hospital (CHUV) has successfully visualized in three dimensions, in a near-natural state, how cytotoxic T-cells attack cancer cells. These immune cells, known as the body's 'killers', eliminate their targets through a contact area called the immunological synapse, where they release toxic molecules in a targeted manner, without affecting the surrounding healthy cells.

Published in Cell Reports, this study reveals for the first time the organization of these mechanisms at the nanoscale within intact human cells. The researchers utilized an innovative technique called cryogenic expansion microscopy (cryo-ExM), which allows for the faithful preservation of cellular structures before observing them with high precision.

The observations particularly show that the membrane of T-cells forms a dome-like structure at the contact point with the target cell, linked to adhesion interactions. The cytotoxic granules, responsible for cell destruction, also exhibit variable organizations, with one or more nuclei concentrating the active molecules.

The team extended this approach to human tumor tissues, allowing for direct observation of T-cells infiltrating tumors and their activity within the very heart of cancers. These advances provide a better understanding of the mechanisms that determine the effectiveness of the immune response and could contribute to improving strategies in immuno-oncology.