TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis

Jan Baijer 1 Nathalie Dechamps 1 Hervé Perdry 2 Pablo Morales 1 Sarah Kerns 3 Alexandre Vasilescu 1 Sylvain Baulande 4 David Azria 5 Paul Roméo 1 Annette Schmitz 1
1 SCSR (U967 / UMR-E_008) - Cellules Souches et Radiations
2 CESP - Centre de recherche en épidémiologie et santé des populations
3 URMC - University of Rochester Medical Center
4 Institut Curie
5 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
Abstract : Sensitivity of T4 effector-memory (T4EM) lymphocytes to radiation-induced apoptosis shows heritability compatible with a Mendelian mode of transmission. Using gene expression studies and flow cytometry, we show a higher TNF-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10)mRNA level and a higher level of membrane bound TRAIL (mTRAIL) on radiosensitive compared to radioresistant T4EM lymphocytes. Functionally, we show that mTRAIL mediates a pro-apoptotic autocrine signaling after irradiation of T4EM lymphocytes linking mTRAIL expression to T4EM radiosensitivity. Using single marker and multimarker Family-Based Association Testing, we identified 3 SNPs in the TRAIL gene that are significantly associated with T4EM lymphocytes radiosensitivity. Among these 3 SNPs, two are also associated with acute and subacute dermatitis after radiotherapy in breast cancer indicating that T4EM lymphocytes radiosensitivity may be used to predict response to radiotherapy. Altogether, these results show that mTRAIL level regulates the response of T4EM lymphocytes to ionizing radiation and suggest that TRAIL/TNFSF10 genetic variants hold promise as markers of individual radiosensitivity.
Keywords : TRAIL acute radiosensitivity apoptosis biomarker lymphocyte
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UNIV-MONTPELLIER | CESP | VALDAURELLE | CURIE | UVSQ | CEA | FNCLCC | BS | IRCM | UNIV-PARIS7 | PSL | USPC | UNIV-PARIS-SACLAY

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Jan Baijer, Nathalie Dechamps, Hervé Perdry, Pablo Morales, Sarah Kerns, et al.. TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis. Oncotarget, Impact journals, 2016, 7 (16), pp.21416-21427. ⟨10.18632/oncotarget.7893⟩. ⟨hal-02294327⟩

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