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Series GSE122934 Query DataSets for GSE122934
Status Public on Apr 13, 2020
Title Cutaneous T cell lymphoma (CTCL) treated with antibiotics and followed over time
Organism Homo sapiens
Experiment type Expression profiling by array
Summary It is unknown why cutaneous T cell lymphoma (CTCL) progress from a relative indolent skin condition to severe cancer with a poor prognosis. Staphylococcus aureus (SA) has been suspected to play a role, because antibiotics have an inhibitory effect on the tumor burden in some patients. As these patients often display skin colonization by SA, it was hypothesized, but never proven, that SA generate a pro-oncogenic milieu in lesional skin. Here, we study the effect of short-term aggressive antibiotic treatment on tumor cells, the microenvironment, and disease activity in treatment-refractory, advanced stage CTCL. We report that advanced stage CTCL patients experienced significant decrease in clinical and patient-self-reported symptoms in response to aggressive 4-week antibiotic therapy, which eradicated SA. Notably, the clinical improvement lasted for more than 8 months in some patients. Global mRNA expression and cell-signaling pathway analysis indicated a decrease in IL-2 signaling, inflammation, and mitosis in skin lesions after antibiotic therapy. In accordance, IL-2 receptor  chain (IL2R-) expression, STAT3 activation, and mitotic activity were decreased in lesional skin following antibiotic treatment. Conversely, SA toxins triggered IL2R- expression, STAT3 activation, and enhanced proliferation ex vivo in primary malignant T cells derived from untreated patients. In conclusion, we demonstrate that transient, aggressive antibiotic treatment inhibits tumor cells, partly normalizes the microenvironment, and decreases disease activity in lesional skin. Thus, we provide a first mechanistic link between antibiotics, skin inflammation, and tumor burden and therefore a novel rationale for treatment of SA in advanced CTCL.
Overall design 8 CTCL patients were followed over time 0, 10 days, 1 month and 2 months. Six healthy controls were used for comparison.
Contributor(s) Litman T, Lindahl LM, Iversen L, Ødum N
Citation(s) 31331920
Submission date Nov 26, 2018
Last update date Apr 13, 2020
Contact name Thomas Litman
Phone 4541851753
Organization name University of Copenhagen
Department ISIM
Street address Blegdamsvej 3C
City Copenhagen N
State/province Outside the US or Canada
ZIP/Postal code 2200
Country Denmark
Platforms (1)
GPL17586 [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version]
Samples (38)
GSM3488850 Pt3-0d
GSM3488851 Pt4-0d
GSM3488852 Pt3-10d
BioProject PRJNA506963

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Supplementary file Size Download File type/resource
GSE122934_RAW.tar 912.1 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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