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L. Zhang

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    MINI 02 - Immunotherapy (ID 92)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI02.13 - Immune Related Gene Signature Reveal Potential Role for Leukocyte-Associated Immunoglobin-Like Receptor 2 (LAIR2) in Lung Cancer Regulation (ID 1243)

      10:45 - 12:15  |  Author(s): L. Zhang

      • Abstract
      • Presentation
      • Slides

      Cancer development and biology is influenced by the host immune system. Emerging data indicate that the context of immune cell infiltrates within the tumor is associated with cancer prognosis. Both the activation state and type of immune cells present can provide mediators that either promote or inhibit tumor growth. While the presence of activated cytotoxic T lymphocytes (CTL) may correlate with better patient survival, the presence of tumor associated macrophages and effector lymphocytes that lack cytotoxic properties may promote tumor growth. Thus, in established tumors, a balance between pro and anti-tumor mediators are present, but as advanced tumors rarely regress without therapeutic intervention, this balance is likely skewed towards tumor-promoting inflammation. In attempts to gain insight into the immune networks that regulate tumorigenesis, we used genome wide gene expression datasets of primary lung cancer tissues to identify and functionally validate immune related genes that are associated with patient survival.

      Gene expression analysis was conducted on microarray datasets from 128 early-stage NSCLC resected tumor samples. Limiting analysis to immune-related gene sets curated by NIAID ImmPortal, we identified a minimum gene set using MAximizing R Square Algorithm (MARSA) that selected for the greatest separation between good and poor prognostic patient subgroups. The prognostic value of this gene signature was validated in nine additional independently published microarray datasets of NSCLC. From the gene signature, we functionally characterized the potential role of the soluble protein LAIR2 in immune regulation of lung cancer.

      We identify a 9-gene signature that separate patients into high and low-risk subgroups for 5-year cancer-free survival (hazard ratio 10.26, 95% confidence interval 4.32-24.34, p<0.0001). The prognostic accuracy of this signature was validated in additional NSCLC datasets (total 1095 patients without adjuvant treatment). Amongst the 9-genes, the gene encoding the soluble protein LAIR2 was highly expressed within the high-risk patient subgroup. Functionally, we found that addition of recombinant LAIR2 resulted in increased NK cell expression of cytotoxicity receptors and secretion of pro-inflammatory cytokines in the presence of lung cancer cell lines.

      By limiting gene expression analysis to immune related genes, we identify a 9-gene prognostic immune signature in resected early stage NSCLC patients. The signature identifies a role for the soluble protein LAIR2 in the modulation of immune cell activation during lung cancer development and may suggest that LAIR2 induce a pro-inflammatory microenvironment which promote tumorigenesis and poor patient outcome.

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