Author of

• 25450

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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
  • Now Available
  • Moderators:G. Scagliotti, F. Skoulidis
  • Coordinates: 4/12/2018, 16:45 - 18:15, Room B

  • 25454

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    1O - Integration of tissue and circulating parameters identifies a favorable immune profile in NSCLC patients treated with nivolumab (Now Available) (ID 421)

    17:30 - 17:45  |  Author(s): A. Ardizzoni
    • 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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