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
4228 - Clinical Evaluation of Drug-Eluting Bead Transcatheter Arterial Chemoembolization(D-TACE) versus Conventional TACE in Treatment of unresectable Hepatocellular Carcinoma
Presenter: Yi Chen
Session: Poster Display session 1
Resources:
Abstract
3930 - Safety profile of tepotinib in patients with advanced solid tumors: pooled analysis of phase I and II data
Presenter: Thomas Decaens
Session: Poster Display session 1
Resources:
Abstract
5373 - Drug-drug interaction profile of tepotinib with CYP3A and P-gp substrates
Presenter: Juergen Heuer
Session: Poster Display session 1
Resources:
Abstract
5455 - Bioavailability of tepotinib: impact of omeprazole and food
Presenter: Juergen Heuer
Session: Poster Display session 1
Resources:
Abstract
2618 - Tislelizumab Exposure-Response Analyses of Efficacy and Safety in Patients with Advanced Tumors
Presenter: Chi-Yuan Wu
Session: Poster Display session 1
Resources:
Abstract
2563 - Population Pharmacokinetics of Tislelizumab in Patients with Advanced Tumors
Presenter: Chi-Yuan Wu
Session: Poster Display session 1
Resources:
Abstract
2021 - The Addition of Metformin to Systemic Anticancer Therapy
Presenter: Jung Han Kim
Session: Poster Display session 1
Resources:
Abstract
5243 - Growth modulation index (GMI) as a comparative measure of clinical activity of larotrectinib versus prior systemic treatments in adult and pediatric TRK fusion cancer patients
Presenter: Antoine Italiano
Session: Poster Display session 1
Resources:
Abstract
598 - Analysis of the overall survival and main surrogates used for FDA approvals in solid and hematological malignancies.
Presenter: Maria Kleniewska-Wieczor
Session: Poster Display session 1
Resources:
Abstract
5381 - Comparison of intratumoral docetaxel exposure in cancer patients between nanoparticle entrapped docetaxel (CPC634) and conventional docetaxel (Cd): the CriTax study
Presenter: Ruben Van Eerden
Session: Poster Display session 1
Resources:
Abstract