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A.J. Bograd

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    MO19 - Lung Cancer Immunobiology (ID 91)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
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      MO19.12 - Prognostic Impact of Tumor-Infiltrating Immune Cells in Lung Squamous Cell Carcinoma (ID 2896)

      10:30 - 12:00  |  Author(s): A.J. Bograd

      • Abstract
      • Presentation
      • Slides

      The prognostic significance of the tumor immune microenvironment in lung adenocarcinoma has been established by us (CCR 2011, JCO 2013, Oncoimmunology 2013) and others. Here, we investigate whether tumor-infiltrating immune cells correlate with prognosis, independent from TNM staging, in lung squamous cell carcinoma (SCC).

      All available tumor slides from therapy-naive, surgically resected solitary lung SCCs (n=485; 1999-2009) were reviewed. Tissue microarrays were constructed using 451 cases (stage I, 255; II, 131; III, 65) from 3 representative tumor areas. Immunostaining for CD3 (pan T cell marker), CD45RO (memory T cell), CD8 (cytotoxic T cell), CD4 (helper T cell), FoxP3 (regulatory T cell), CD20 (B cell), CD68 (macrophage), and CD10 (neutrophil) was performed. For each case, the average number of cells positive for T cell markers was recorded as the ratio to CD3+ lymphocytes, and classified as low or high by use of the median. CD20, CD68, and CD10 were classified as low or high by the number of positive cells (≥20, ≥50, and ≥10, respectively) as our recent publication (JCO 2013). Overall survival (OS) was estimated using the Kaplan-Meier method; multivariate analyses were performed using the Cox proportional hazards model.

      Five-year OS was 59% for the entire cohort and 68% for stage I patients. Analysis of single immune cell infiltration revealed that high CD10+ neutrophil count was correlated with lower OS (5-year OS, 53%; n=160) than low CD10+ count (5-year OS, 61%; n=286; p=0.006). Analysis of biologically relevant immune cell combinations identified 2 significant factors of prognosis: (1) patients with high CD4+ and high FoxP3+ T cell ratios had worse prognosis (5-year OS, 52%; n=140) than the other groups (5-year OS, 62%; n=304; p=0.008), and (2) patients with high CD10+ neutrophil and low CD20+ B lymphocyte counts had worse prognosis (5-year OS, 43%; n=102) than the other groups (5-year OS, 63%; n=340; p<0.001). These results were confirmed in a subgroup analysis limited to stage I patients (p=0.020 for high CD4/high FoxP3+ ratios; p=0.007 for high CD10+/low CD20+ counts). In multivariate analysis, high CD4+/high FoxP3+ ratios (HR=1.58; p=0.001) and high CD10+/low CD20+ counts (HR=1.71; p<0.001) remained significantly associated with poorer survival (Table).

      Table. Multivariate analysis for overall survival
      Variable HR 95% CI p
      High CD4+/high FoxP3+ ratios 1.58 1.21–2.06 0.001
      High CD10+/low CD20+ counts 1.71 1.28–2.27 <0.001
      Age (>65 years old) 1.51 1.09–2.09 0.014
      Sex (male vs. female) 1.31 1.01–1.69 0.043
      Smoking pack years (>90) 1.01 1.00–1.01 0.003
      Stage (II and III vs. I) 1.53 1.16–2.02 0.002
      Lymphovascular invasion 1.38 1.02–1.88 0.040

      High CD4+/high FoxP3+ ratios and high CD10+/low CD20+ counts are significant factors of prognosis for lung SCC, independent of TNM staging. Targeting regulatory T cells or enhancing tumor-specific B-cell responses may thus have applicability for the treatment of lung SCC.

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