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• 12413

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  P3.04 - Poster Session 3 - Tumor Immunology (ID 155)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12416

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    P3.04-003 - High levels of circulating immunosuppressive cells predict worst clinical outcome in Non-Small Lung Cancer (NSCLC) patients (ID 2665)

    09:30 - 09:30  |  Author(s): A. Koutoulaki
    • Abstract

    Background
    The immune cells can prevent and inhibit tumour development but also may contribute to growth and progression of cancer. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature cells with immune suppressive properties, have been correlated with worse prognosis in several tumors. In addition, high levels of circulating CD4[+] T regulatory (Tregs) cells exhibit suppressive functional activity against anti-tumour T-cell responses and correlated with worse recurrence-free survival in NSCLC patients. In the present study, we investigated the expression and levels of MDSCs’ subpopulations and CD4[+]Tregs, their correlation to distinct immune cells, as well as to the clinical outcome of patients with advanced NSCLC.

    Methods
    Peripheral blood from 112 chemotherapy-naive patients with stage III/IV NSCLC and 27 healthy donors was analyzed with flow cytometry for the presence of monocytic and granulocytic subpopulations of MDSCs, CD4[+ ]Tregs, as well as the frequencies of distinct immune cells such as CD4[+ ]and CD8[+ ]cells, dendritic cells (DC) and B cells. The frequencies of these cells in the patients were compared to the healthy donors. The patients’ clinical outcome (PFS and OS) was compared according to the frequency of MDSCs and Tregs (high vs low expression as defined by their percentage above healthy donors).

    Results
    Two monocytic (CD14[+]CD15[-]CD11b[+]CD33[+]HLA-DR[-]Lin[-] and CD14[+]CD15[+]CD11b[+]CD33[+]HLA-DR[-]Lin[-]), and a granulocytic (CD14[-]CD15[+]CD11b[+]CD33[+]HLA-DR[-]Lin[-]) subpopulations as well as CD4[+] Tregs (CD3[+]CD4[+]CD25[+high]CD152[+]CD127[-]Foxp3[+]) were increased in patients compared to healthy donors (p<0.001 and p<0.007, respectively). Levels of MDSCs and CD4+ Tregs did not associated with tumor histology or stage of the disease. The levels of both subpopulations of monocytic but not of granulocytic MDSCs were reversely correlated with the levels of dendritic cells (DC) (r[2]=-0.3, p≤0.04) whereas the granulocytic subpopulation of MDSCs was reversely correlated with the levels of CD4[+] T cells (r[2]=-0.3, p=0.006). Increased baseline levels of both monocytic MDSCs’ subpopulations was associated with early relapse despite front-line platinum-based chemotherapy (p=0.05). The detection of baseline CD14[+]CD15[+]CD11b[+]CD33[+]HLA-DR[-]Lin[-] MDSCs within the normal levels was associated with longer OS compared to those with high levels (p=0.0035). Finally, patients with normal CD4[+ ]Tregs frequencies had a higher OS than those with high frequencies (p=0.05).

    Conclusion
    The data show that increased levels of monocytic MDSCs and CD4[+] Tregs in the peripheral blood of NSCLC patients are reversely correlated to the other normal immune cells. These cells could represent potential predictive/prognostic biomarkers since their increased levels were negatively correlated to the treatment outcome.