Author of

• 18502

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  P3.02c - Poster Session with Presenters Present (ID 472)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18605

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    P3.02c-103 - Effect of Anti-PD-1 Therapy on Immune Cells in the Peripheral Blood of Non-Small Cell Lung Cancer (NSCLC) Patients (ID 5869)

    14:30 - 14:30  |  Author(s): Z. Lyristi
    • Abstract

    Background:
    Programmed cell death-1 (PD-1), plays a pivotal role in tumor immune escape. Recently, antibodies targeting PD-1 and PD-L-1 have been approved for treatment of advanced Non Small Cell Lung Cancer (NSCLC). In this pilot study, we aimed to investigate the effect of anti-PD1 treatment or chemotherapy on the frequencies of circulating PD-1[+] T cells and PD-L1[+] immunosuppressive cells in NSCLC patients.
    
    Methods:
    Peripheral blood samples were collected from 35 advanced NSCLC patients before initiation of treatment and after 3 cycles. Twelve treatment-naïve patients received front-line chemotherapy, whereas 23 patients received anti-PD1 treatment in the second-line setting. Flow cytometry was used to quantify PD-1- and PD-L1-expressing immune cells. Changes in the frequencies of these cells were compared between the two settings and correlated with the clinical outcome.
    
    Results:
    Chemotherapy had no effect on the percentages of PD-1[+]CD4[+] and PD-1[+]CD8[+] T cells after 3 cycles, whereas there was a significant decrease in PD-1[+]CD4[+] and PD-1[+]CD8[+] T cells in patients who received 3 administrations of anti-PD1 antibody (p=0.007 and p=0.05, respectively). Moreover, the levels of PD-1[-]CD4[+] (p=0.009) and PD-1[-]CD8[+] (p=0.009) were increased in response to anti-PD-1 therapy. The frequencies of both peripheral CD4[+] Treg (CD3[+]CD4[+]CD25[high]CD127[-/low]CD152[+]FoxP3[+]) and granulocytic MDSCs (G-MDSC; CD14[-]CD15[+]CD33[+]CD11b[+]HLA-DR[-]Lin[-]) expressing PD-L1 were decreased following anti-PD1 therapy (p=0.01 and p=0.02, respectively). In contrast, after 3 cycles of chemotherapy, the levels of PD-L1[+]CD4[+] Treg were increased, but not of the PD-L1[+]G-MDSC (p=0.04). Anti-PD-1 treatment significantly reduced the percentages of PD-1[+]CD4[+], PD-1[+]CD8[+] T cells, PD-L1[+]CD4[+] Treg and PD-L1[+]G-MDSCs when compared to the effect of first line chemotherapy (p=0.04, p=0.05, p=0.002 and p=0.01, respectively). Furthermore, a significant decrease of PD-1[+]CD8[+] T cells, PD-L1[+]CD4[+] Treg and PD-L1[+]G-MDSCs after 3 doses of anti-PD-1 was observed in patients who experienced stable disease compared to baseline (p=0.006, p=0.05 and p=0.03, respectively). At the time of response evaluation to chemotherapy, the percentage of the PD-L1[+]CD4[+] Treg after 3 cycles was significantly decreased compared to baseline, in disease progressors (p=0.04).
    
    Conclusion:
    Treatment with anti PD-1 antibodies significantly reduces the levels of PD-1+ effector cells, as well as the PD-L1+ suppressive Treg and G-MDSCs. In contrast chemotherapy led to an increase of PD-L1+ Treg. These data indicate that treatment with anti-PD1 agents have an overall positive effect on immune system by reducing the immunosuppressive cells and increasing the effector cells. Additional studies are needed in a larger cohort in order to document its impact on their clinical relevance in NSCLC patients.