Author of

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  P2.03 - Biology (ID 162)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30788

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    P2.03-08 - Analysis of Immunosuppressive Factors Produced by CSCs Revealed Galectin-3 as Immune Modulator with Prognostic Value in NSCLC Adenocarcinoma (ID 1855)

    10:15 - 18:15  |  Author(s): Javier Garde
    • Abstract

    Background
    

    The study of the tumor microenvironment is leading to a better understanding of the tumor escape from immunosurveillance and immunotherapy response. Cancer stem cells (CSCs) are targets poorly recognized by the immune surveillance system given that they favor an immunosuppressive microenvironment. The aim of this work is to study the interactions between CSCs and the immune microenvironment in NSCLC.

    Method
    

    Tumor cells from 8 resected NSCLC patients and 12 cell lines were cultured using a sphere forming assay for CSCs enrichment. Adherent cultures were established as differentiated controls. The gene expression of IL-4, IL-10, IL6, IL8 LGALS-3 was analyzed by RTqPCR. Gene expression results were validated at a protein level by a sensitivity bead-based multiplex immunoassay using the Millipore kit for Luminex 100/200. The prognostic value of these factors in silico was determined in a cohort of 661 patients from The Cancer Genome Atlas (TCGA) cohort. Prognostic value was assessed by Cox regression and Kaplan‐Meier curves ﴾long rank‐test﴿, considering significant when p<0.05.

    Result
    

    Patients’ median age was 67 years [57-74], 62% were male, and 62.5% were adenocarcinomas (ADC). Gene expression analysis revealed that lungspheres had significantly higher expression of LGALS3 compared to differentiated adherent cells. On the contrary, adherent cells had significantly higher expression of IL6. In concordance with gene expression levels, we observed significant differences in the secretion of these two soluble factors (IL-6 and Galectin-3) between adherent cells and tumorspheres. Neither expression nor secretion levels of IL-10 and IL-4 were detectable. We had not observed significant results for IL-8. Survival analysis showed that ADC patients with higher LGALS3 expression had significantly decreased overall survival (OS, 40.49 vs. 87.90 months, p= 0.005) and relapse-free survival (25.28 vs. 41.25 months, p=0.003) than the group with LGALS3 expression below the median. The multivariate analysis showed that LGALS3 expression can be established as an independent prognostic biomarker for OS [HR=1.75; 95% CI, 1.19-2.59; p=0.004] and for PFS in lung adenocarcinoma [HR=1.68; 95% CI, 1.22-2.32; p= 0.001].

    Conclusion
    

    Our results suggest that Galectin-3 highly secreted by lung CSCs can be involved in the modulation of the immune microenvironment. Moreover, Galectin-3 is an independent prognostic biomarker for overall survival and relapse-free survival in lung adenocarcinomas.

    Supported by grants CB16/12/00350, PI18/00266 and PI15-00753 from ISCIII and ACIF/2018/275 from GVA and FSE