1314 - Assessment of the predictive/ prognostic value of the myeloid-derived suppressor cells (MDSC) and regulatory T cells (TREGs) in non-small cell lung...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter E Vetsika
Authors E.K. Vetsika1, E. Skalidaki1, A. Koutoulaki1, D. Mavroudis2, V. Georgoulias2, A. Kotsakis2
  • 1Laboratory Of Tumor Cell Biology, University of Crete, School of Medicine, 71110 - Heraklion/GR
  • 2Medical Oncology, University Hospital of Heraklion, 71110 - Heraklion/GR

Abstract

Background

The circulating MDSCs and Tregs in cancer patients suppress immune system. This study is investigating the expression of the MDSCs and Tregs in the peripheral blood of NSCLC patients and their correlation with the clinical outcome of the 1st line chemotherapy.

Methods

62 chemotherapy naive patients (57 males) with stage IIIB/ IV NSCLC have been enrolled in this study, so far; median age 67. Peripheral blood was collected prior to treatment. 19 healthy, aged-matched donors (12 males) were used as controls. The distinct MDSC subpopulations [A (monocytic): CD11b+CD14+CD15CD33+CD13+IL-4R+Linlow/-HLA-DR; B (monocytic): CD11b+CD14+CD15+CD33+CD13+IL-4R+Linlow/-HLA-DR and C (granulocytic): CD11b+CD14CD15+CD33+ CD13+IL-4R+)], CD4+ Tregs (CD4+CD25+high CD127low FoxP3+CD39+CD13+) and CD8+ Tregs (CD3+CD8+CD25+ CD45RO+CD13+CCR7+FoxP3+CD39+) were determined by using flow cytometry. A comparison of the overall survival (OS) and the progression-free survival (PFS) according to the frequency of the MDSC and Tregs was performed (high expression defined as the percentage of cells above the 75% percentile of the controls).

Results

The levels of Tregs prior to treatment did not differ from the controls'. Patients with progression (PD) during the 1st line treatment had significantly elevated percentage of CD4+ (24.6 ± 8.5) and CD8+ (0.7± 0.2) Tregs at baseline compared to those with no PD (3.7± 1.8, p = 0.04; 0.1± 0.05, p= 0.03, respectively). In contrast, MDSCs were significantly increased (A: 3.8 ±0.7; &Bgr;: 2.5 ± 0.5 and C: 10.8 ± 2.3) in patients compared to controls (0.8 ± 0.4, p = 0.001; 0.5 ± 0.2, p= 0.01, and 2.7 ± 1.3, p= 0.05, respectively) but that difference was not associated with response to treatment. Patients with normal CD8+ Tregs levels at baseline had higher OS and PFS compared to those with high levels (13.2 mo vs 7.9 mo, p= 0.02 and 13.1 mo vs 3.7 mo, p= 0.003, respectively).

Conclusion

The MDSCs are elevated in NSCLC. The increased expression of CD4+ ?α&igr; CD8+ Tregs negatively correlated with the treatment outcome, indicating that CD4+ and CD8+ Tregs could be a potential predictive/prognostic biomarker. The study is still opened to accrual and more mature data will be presented at the meeting.

Disclosure

All authors have declared no conflicts of interest.