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| Identifier |
000388696 |
| Title |
Definition and clinical implication of human foxP3+ CD4+ treg cell subsets in non-small cell lung cancer patients |
| Alternative Title |
Προσδιορισμός των υποτύπων των foxP3+CD4+T ρυθμιστικών κυττάρων και συσχέτιση τους με την κλινική εικόνα των ασθενών με μη μικροκυτταρικό καρκίνο του πνεύμονα |
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Author
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Κατσαρού, Αφροδίτη
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Thesis advisor
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Μαυρουδής, Δημήτριος
Βέτσικα, Ελένη-Κυριακή
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Reviewer
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Γεωργούλιας, Βασίλης
Κωτσάκης, Αθανάσιος
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| Abstract |
Regulatory T cells (Tregs) play an important role in the modification of immune responses in malignancy. Treg population presents a high degree of heterogeneity, therefore several markers allow the identification of phenotypically distinct Treg subsets which present different functional characteristics. However, little is known the different subtypes of the regulatory T cells (Tregs) in the peripheral blood of non-small cell lung cancer (NSCLC) patients. The aims of this study were to determine the phenotypic and functional characteristics of different circulating Treg subtypes in the peripheral blood in NSCLC patients and the significant effect of therapy on the frequency of the circulating Tregs subset was also investigated.
Peripheral blood was collected from 145 treatment-naïve NSCLC patients and 31 aged-matched heathy donors, as well as the 3rd and the 6th cycle of treatment. The presence of circulating Treg subsets was examined by studying the presence of intra- and extracellular markers in whole blood using flow cytometry. The functionality of these cells was tested after their isolation from PBMCs, using magnetic separation.
The results showed that the frequencies of CD3+CD4+CD25+high Tregs in NSCLC patients were significantly higher than in normal controls exhibiting a highly suppressive activity. The percentage of the Terminal Memory Effector Treg cells (CCR7- CD25+highCD127-CD152+FOXP3+CD45RO+) was significantly higher in baseline, in NSCLC patients, compared to normal control. Furthermore, higher percentage of Terminal Memory Effector Treg cells was associated with improved prognostic value. Moreover, the levels of Terminal effector (CD25+highCD127-CD152+FOXP3+CD45RO+) and Terminal Memory Effector Treg cells (CCR7-CD25+highCD127-CD152+FOXP3+CD45RO+) increased after the chemotherapy treatment which was associated with an improved prognosis. In contrast, percentage of the Naïve Treg cells (CCR7+ CD25+highCD127-/lowCD152-FOXP3+lowCD45RO-) was significantly higher in baseline, in NSCLC patients, compared to normal control, which was associated with poor prognostic value. Moreover, the levels of Naïve Treg cells increased after the chemotherapy treatment and were correlated with poor clinical outcome.
In conclusion, this thesis has clearly demonstrated, for the first time, two opposite faces of CD4+ Treg cells in respect to clinical outcome, depending on their maturation status. The use of depletion or blocking their migration in the tumour sites may be an effective strategy.
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| Language |
English |
| Subject |
Clinical outcome |
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NSCLC |
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Regulatory T cell suptypes |
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Κλινική εικόνα |
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Μη μικροκυτταρικός καρκίνος του πνεύμονα |
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Υπότυποι Τ ρυθμιστικών κυττάρων |
| Issue date |
2014-12-04 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Views |
199 |
Definition and clinical implication of human foxP3+ CD4+ treg cell subsets in non-small cell lung cancer patients
