Abstract 5547
Background
Cancer stem cells (CSCs) are targets poorly recognized by the immune surveillance system given that they induce an immunosuppressive microenvironment. The aim of this work is to study the interactions between CSCs and the immune microenvironment in NSCLC.
Methods
Tumor cells from 8 resected NSCLC patients and 12 cell lines were established as tumorspheres enriched in CSCs and as monolayers. The gene expression of IL-4, IL-10, IL6, IL8 and LGALS-3 was analyzed by RTqPCR. 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). Prognostic value was assessed by Cox regression and Kaplan‐Meier curves (long rank‐test).
Results
Patients’ median age was 67 years [57-74], 62% were male, and 62.5% were adenocarcinomas (ADC). Gene expression analysis revealed that LGALS3 was significantly higher expressed in lung tumorspheres. By contrast, adherent cells had significantly higher expression of IL6. In accordance 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. No significant results were observed for IL-8, IL-10 and IL-4 expression and secretion. Survival analysis showed that ADC patients with higher LGALS3 expression decreased overall survival (OS, 40.49 vs. 87.90 months, p = 0.005) and relapse-free survival (RFS, 25.28 vs. 41.25 months, p = 0.003) than the group with LGALS3 expression below the median. The multivariate analysis reported 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].
Conclusions
The secretion of Galectin-3 by Lung CSCs may be involved in the modulation of the immune microenvironment. 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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fundación Hospital General Universitario de Valencia.
Funding
CB16/12/00350, PI18/00266 and PI15-00753 from ISCIII and ACIF/2018/275 from GVA and FSE.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5011 - LCSCAF1 maintains cancer stem-like traits by stabilizing c-Myc protein and promotes metastasis and recurrence in lung cancer
Presenter: Tao Guo
Session: Poster Display session 1
Resources:
Abstract
4955 - XAF1 Enhances Temozolomide Induced Autophagic Cell Death through AMPK signaling pathway
Presenter: Mingoo Lee
Session: Poster Display session 1
Resources:
Abstract
5616 - The effect of cortisol on methylation patterns in breast cancer cell lines
Presenter: Haya Intabli
Session: Poster Display session 1
Resources:
Abstract
4649 - Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a Mediterranean population
Presenter: Judith Begona Ramirez Sabio
Session: Poster Display session 1
Resources:
Abstract
4984 - Whole transcriptomics analyses of mimicking Circulating Tumor Cells (CTCs) by single-cell RNA sequencing (scRNAseq)
Presenter: Jessica Garcia
Session: Poster Display session 1
Resources:
Abstract
5926 - Comparison of enzymatic- and bisulfite conversion to map the plasma cell-free methylome in cancer
Presenter: Nicole Lambert
Session: Poster Display session 1
Resources:
Abstract
5454 - Detection of low mutations in hepatocellular carcinoma by using circulating tumor DNA
Presenter: Esl Kim
Session: Poster Display session 1
Resources:
Abstract
4428 - Variants in the JAK1 and JAK2 genes in the risk and prognosis of patients with cutaneous melanoma
Presenter: Bruna Carvalho
Session: Poster Display session 1
Resources:
Abstract
4409 - P-Rex1 expression in breast cancer patients.
Presenter: Angela Lara Montero
Session: Poster Display session 1
Resources:
Abstract
4185 - Modulation of Risk of Cutaneous Melanoma Patients by Variants in STAT3 Gene and Functional Analysis
Presenter: Gabriela Gomez
Session: Poster Display session 1
Resources:
Abstract