T4EM [1]
lymphocytes are lymphocytes that constitute a part of the “memory” of a
person’s immune system. Using a simple radiosensitivity test [2]
on these cells in 373 individuals, scientists at the Institute of Cellular and
Molecular Radiation Biology showed that, without irradiation, the TRAIL[3]
gene, which regulates cell death, was strongly expressed in radiosensitive T4EM
lymphocytes and weakly expressed in radioresistant T4EM lymphocytes.
Using functional studies, these scientists
showed that the TRAIL protein receptor was activated after irradiation and that
the interaction between TRAIL and its receptor killed T4EM lymphocytes. These
results explain the correlation between the level of expression of TRAIL in
T4EM lymphocytes and their radiosensitivity.
A study of the genetic link between TRAIL
and the radiosensitivity of T4EM lymphocytes has identified three single
nucleotide polymorphisms (SNP) of this gene related to the radiosensitivity of
these lymphocytes. This indicates that this radiosensitivity is genetically
determined. Finally, the study of a cohort of 113 breast cancer patients who
developed complications after radiotherapy showed a correlation between two of
the SNPs of the TRAIL gene and the onset of acute or subacute radiation-induced
dermatitis after radiotherapy.
This pioneering study shows how genetics,
associated with functional cellular radiosensitivity tests, can open up the
possibility of personalising the dose delivered when treating cancer by
radiotherapy.