Scientists at the CEA’s Institute of Cellular and Molecular Radiation Biology, in collaboration with INSERM, Université Paris-Sud, and international partners, have demonstrated a connection between the expression of the TRAIL gene, which plays a role in cell death, and the radiosensitivity of certain human T lymphocytes. This research also showed a relationship between three genetic forms of TRAIL and the radiosensitivity of these T lymphocytes. Finally, two of these genetic forms of TRAIL were linked with serious skin complications in breast cancer patients treated with radiotherapy. These results, published on the Oncotarget website on 16^th March 2016, indicate how determining the radiosensitivity of lymphocytes and studying the gene polymorphisms associated with this radiosensitivity could lead to personalised radiotherapy. 

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.

© P.Stroppa / CEA

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.

[1] Lymphocyte T4 effector-memory

[2] This test uses flow cytometry to quantify the death of T4EM lymphocytes according to the irradiation dose to which they have been subjected.

[3] TNF-Related Apoptosis Inducing Ligand

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