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TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis. Oncotarget 2016 Apr 19;7(16):21416-27

Date

03/17/2016

Pubmed ID

26982083

Pubmed Central ID

PMC5008295

DOI

10.18632/oncotarget.7893

Scopus ID

2-s2.0-84965010117 (requires institutional sign-in at Scopus site)   12 Citations

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.

Author List

Baijer J, Déchamps N, Perdry H, Morales P, Kerns S, Vasilescu A, Baulande S, Azria D, Roméo PH, Schmitz A

Author

Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Disease
Apoptosis
CD4-Positive T-Lymphocytes
Dermatitis
Flow Cytometry
Gene Expression
Genotype
Humans
Polymorphism, Single Nucleotide
Radiation Tolerance
Radiation, Ionizing
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Skin
TNF-Related Apoptosis-Inducing Ligand