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G. Missale



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    PD-L1 expression and tumor microenvironment in advanced lung cancer (ID 59)

    • Event: ELCC 2018
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      1O - Integration of tissue and circulating parameters identifies a favorable immune profile in NSCLC patients treated with nivolumab (ID 421)

      16:45 - 18:15  |  Author(s): G. Missale

      • Abstract
      • Presentation
      • Slides

      Background:
      To define prognostic and potentially predictive immune profiles in NSCLC patients receiving nivolumab, an integrated analysis of tissue and circulating parameters was performed.

      Methods:
      Peripheral blood (PB) from 31 advanced NSCLC patients was analyzed by FACS to assess CD3, CD8, CD4, NK, Treg, and MDSC (CD14[pos]/CD33[pos]/DR[neg]) number, function (PD-1, CD3ζ, Granzyme B, Perforin) and proliferation (Ki67). Data were collected at baseline (T0), and after 2 (T1) and 4 (T2) cycles of bi-weekly nivolumab. PD-L1 (H-score) and TILs subpopulations were immunohistochemically investigated. Merged tissue and circulating parameters were correlated to clinico-pathological features, response to treatment (RECIST 1.1) and survival outcomes.

      Results:
      T cells were more represented in PB from ADC patients (p < 0.01 vs SqCC), while KRAS mutation conditioned higher number of CD3, CD8, CD4, and NK, and lower MDSC (p < 0.05). Active smoking and BPCO directly correlated with T and NK cells proliferation (p < 0.05). Additionally, steroid naïve patients had increased effector and reduced immune suppressive (p < 0.05) phenotypes. Clinical benefit (CB, n = 19) group, compared to non-responder (NR, n = 12), displayed a distinctive PB immune profile at baseline, including higher NK (tot, CD3ζpos, Pfnpos, GrzBpos) and CD8pos/PD-1pos cells (p < 0.01). These CB immune features were maintained during nivolumab, while MDSC progressively rose in NR (p < 0.05). Prolonged OS (p < 0.05) and PFS (p < 0.01) were recorded in cases with high NK and CD8pos/PD-1pos number at T0. At tissue level, while high PD-L1 score had a modest clinical impact, low PD-1 expression in CD8pos TILs was a distinctive feature of CB (p < 0.001 vs NR) and correlated with better OS (ns) and PFS (p < 0.01). Strikingly, the combination of predetermined PB (high NK and CD8pos/PD-1pos) and tissue (low CD8pos/PD-1pos) positive prognostic factors characterized an immune privileged context provided by significantly prolonged PFS (p < 0.001) and OS (p < 0.01).

      Conclusions:
      A divergent PD-1 expression in blood and tissue cytotoxic cells associated with a preserved functional pool of circulating NKs portrays an immune profile prone to nivolumab efficacy.

      Clinical trial identification:


      Legal entity responsible for the study:
      University of Parma, Italy

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

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