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M. Inomistova



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      70P - Immunological efficacy of anti-tumor dendritic cell vaccine application in patients with non-small cell lung cancer (ID 410)

      12:30 - 13:00  |  Author(s): M. Inomistova

      • Abstract

      Background:
      Immunotherapy using dendritic cells (DC) represents a novel and promising therapeutic method for patients with non-small cell lung cancer (NSCLC). The aim was to examine the molecular and cellular mechanisms of anticancer immune responses during immunotherapy as well identify the immune parameters that may predict DC vaccine therapy efficiency.

      Methods:
      One hundred patients with IIB-IIIA stage NSCLC were enrolled into the study. Patients were randomly allocated into two groups: 1st – patients received DC-vaccine after surgery, 2nd – received surgery only. Original construction of DC vaccine has been used: autologous DCs with mechanically heterogenized microparticles of tumor cells. Patients received four intravenous injections with one-month interval and immunological monitoring was performed before each injection.

      Results:
      The most notable changes in cell-mediated immune response was observed after the 4[th] injection of DC vaccine. Namely, the balance of Th1- and Th2-mediated immune response was changed, in particular the number of CD3[+]IFN-γ[+] lymphocytes prevailed over CD3[+]IL-4[+] lymphocytes. Moreover, the CD4[+]CD45RO[+] memory cell numbers increased in peripheral blood and the TGF-β mRNA expression level was significantly decreased in circulating leucocytes (p < 0.05) compared with that in patients without DC-vaccine treatment. According to Cox proportional hazard model, changes in the number of CD4[+]CD45RO[+] memory cells (p < 0.05), TGF-β mRNA expression level (p < 0.02) and ratio of CD3[+]IFN-γ[+] lymphocytes to CD3[+]IL-4[+] lymphocytes (p < 0.02) allow us reliably to determine the development of relapses in patients with NSCLC. Using ROC analysis, we established the optimal criteria for these immunological markers, which can separate groups by low and high risk of NSCLC recurrence: <0.74 for ratio of CD3[+]IFN-γ[+] lymphocytes to CD3[+]IL-4[+] lymphocytes (p < 0.001, AUC = 0.92, Se = 100%, Sp = 75%); ≤0.62 × 10[3] cells/mL for CD4[+]CD45RO[+] memory cells (p < 0.001, AUC = 0.91, Se = 100%, Sp = 82%); >0.034 a.u. for TGF-β mRNA expression (p < 0.05, AUC = 0.73, Se = 67%, Sp = 100%).

      Conclusions:
      Immunological markers with prognostic significance regarding the duration of the event-free period have been established in patients with NSCLC after DC vaccine treatment.

      Clinical trial identification:


      Legal entity responsible for the study:
      National Cancer Institute of the MPH Ukraine

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.