Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first-line chemotherapy
التفاصيل البيبلوغرافية
العنوان:
Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first-line chemotherapy
Background In humans Tregs lack a unique phenotypic marker and Foxp3 expression in cluster of differentiation (CD) 4+CD25+ or CD4+CD25high T lymphocytes is commonly used for their characterization. In early colorectal cancer, the presence of Tregs in CRC tumour tissue has been associated with favourable prognosis. However, the prognostic role of circulating Tregs in CRC patients and especially in the metastatic setting is not yet clear. Methods We collected peripheral blood from 57 patients with mCRC before initiation of first line chemotherapy. Samples were analysed with multicolour flow cytometry using monoclonal antibodies against CD3, CD4, CD25, and FoxP3. The ratio of FoxP3 positive cells within the CD3+CD4+CD25high lymphocytic subpopulation (F/H ratio) was measured and quartile analysis according to this ratio was carried out. Overall survival was calculated from initiation of first line chemotherapy to death or last follow up. Median OS (mOS) was compared between the highest quartile and the rest using the Breslow (Generalized Wilcoxon) method. Ratios were compared between groups with the Mann Whitney U-test. Statistics were analyzed with SPSS and flow cytometry data with Kaluza 2.1. Results The median F/H ratio was 0,08 (Interquartile range 0,018-0,34) with a distribution skewed to the right (range 0 to 0.85). For each quartile mOS is shown in the table. The mOS for the highest quartile was 8 months (m) (95% Confidence Interval(CI) 0 - 20.6m) and 25m for the rest (95% CI 18.2m-31.8m)(p = 0.03). No difference was observed in F/H ratio in different groups according to KRAS/NRAS mutations’ status, prior adjuvant chemotherapy, performance status or sidedness of primary site. Table . 610P Quartile F/H ratio (range) n mOS (m) mOS(m) p 1st 0-0,018 14 24 25 2nd 0,0181-0,08 15 34 3rd 0,0810-0,34 15 24 4th 0,3410-0,85 13 8 0.03 Conclusions The F/H ratio in patients with mCRC is spread over a wide range of values with the majority below 0.1. High values (>0.34) seem to have prognostic significance and be associated with worse outcome. Legal entity responsible for the study Medical School, University of Crete. Funding Hellenic Oncology Research Group, Medical School, University of Crete. Disclosure Z. Zafeiriou: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Bristol. A. Koutoulaki: Full / Part-time employment: Genesis Pharma. V. Georgoulias: Travel / Accommodation / Expenses: Sanofi. All other authors have declared no conflicts of interest.
