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
1851 - Nivolumab-induced and radiation recall pneumonitis in patients with non-small cell lung cancer: a multicenter real world analysis of 669 patients
Presenter: Nobuaki Mamesaya
Session: Poster Display session 1
Resources:
Abstract
851 - Retrospective analysis of immunotherapy prognostic scores in advanced NSCLC at Nottingham University Hospitals (UK)
Presenter: Cristina Lopez Escola
Session: Poster Display session 1
Resources:
Abstract
3639 - Applicability of lung immune prognostic index (LIPI) to predict efficacy of first-line pembrolizumab in advanced non-small-cell lung cancer (NSCLC)
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 1
Resources:
Abstract
2950 - Delayed Onset Immune Related Adverse Effects (IRAEs) of Pembrolizumab in Non-Small Cell Lung Cancer
Presenter: Haixi Yan
Session: Poster Display session 1
Resources:
Abstract
3659 - Clinical implication of multiplex IHC and serologic biomarkers on Hyperprogression in NSCLC patients receiving Immune checkpoint blockers in real world.
Presenter: Joori Kim
Session: Poster Display session 1
Resources:
Abstract
4882 - Local ablative treatment and treatment beyond progression for oligo-progression in stage IV non-small cell lung cancer after tumor response to anti-PD1 treatment
Presenter: Florian Guisier
Session: Poster Display session 1
Resources:
Abstract
1358 - Atezolizumab in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs)
Presenter: Francis Mogollon-Duffo
Session: Poster Display session 1
Resources:
Abstract
2170 - Prognostic Impact of Metastatic Sites for Pembrolizumab Efficacy as First-line therapy in Patients with PD-L1 tumor proportion score (TPS) ≥ 50% Advanced Non–Small Cell Lung Cancer: A Retrospective Multicenter Study
Presenter: Hayato Kawachi
Session: Poster Display session 1
Resources:
Abstract
3051 - Impact of visceral fat area as independent predictive factor in patients with advanced non-small cell lung cancer treated with nivolumab
Presenter: Yuki Sato
Session: Poster Display session 1
Resources:
Abstract
3409 - Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
Presenter: Toshihiko Iuchi
Session: Poster Display session 1
Resources:
Abstract