Chromosomes are capped by a particular sequence of DNA at each of their ends, known as telomeres. The latter shorten with age, inflammation and stress. When telomeres cease to be long enough, cell division stops and the cell dies – but not always. This is because cancerous cells manage to maintain the telomeres, becoming immortal. Known to protect telomeres, the protein TRF2 is one of the reasons for this longevity.

According to a study by the ENS-Lyon, who benefited from the CEA-IRCM’s expertise in cytogenetics, the action of TRF2 does not stop there. This protein also appears to indirectly reduce the recruitment and activation of certain immune system cells known as natural killers (NK). TRF2 would thus have a double oncogenic role in assuring the longevity of cancerous cells, while preventing the immune system from fighting against them. The researchers have revealed its partner in the latter role as HS3ST4. This protein is activated by TRF2 to block the recruitment of NK cells and to prevent the body’s defenses from coming into play.

This work required a very multidisciplinary approach. The CEA-IRCM conducted studies on telomere instability and chromosomal abnormalities. This way, it contributed to the characterization of models allowing the distinction between the functions of telomere maintenance and of immune system activation.