Abstract 5336
Background
Lung cancer stem cells (CSCs) are a small subpopulation of cells with self-renewal, tumorigenic properties and the ability to grow to form tumorspheres in non-adherent conditions. Recently, the study on soluble molecules has been a new focus to understand the interaction between CSCs and tumor microenvironment. The aim of this work is to compare the release of cytokines between monolayer cells and tumorspheres of NSCLC cultures.
Methods
The study was performed on medium supernatant of cells from 8 NSCLC tumour patients samples and 10 cell lines (A549, H1650, H460, H23, H358, H2228, HCC827, PC9, H1993, SW900) grown in monolayer and tumorspheres at 2 different densities (104 and 105 cells/ml); supernatant was recollected at 12h and 24h. We analyzed 8 soluble factors with immunosuppressive (IL-4, IL-10, IL-13), and immunoregulatory (IL-6, IL-8, IL-17A, TNFa, IFN) capacity through sensitivity bead-based multiplex assay using the Millipore kit from the Luminex 100/200.
Results
IL-4, IL-6, IL-8, TNFa levels were detected in all samples while IFN, IL-10, IL-13, IL-17A were beyond the detectable range in adherents for most of cultures (Detection range [pg/ml] of IL-4: 1.83-7497.38, IL-6: 0.18-813.66, IL-8: 0.31-1042.75, TNFa: 0.43-1758.47, IFN: 0.61-2468.39, IL-10: 1.46-6056.85, IL-13: 0.24-1002.76, IL-17A: 0.73-3074.88). We observed significant differences in levels of IL-6, IL-13, IL-17A, TNFa, IFN between adherent cells and tumorspheres. Moreover, IL-4, IL-10, IL-13, IL-17A, IFN levels in tumorspheres were higher than monolayer. Otherwise, IL-6 and TNFa were secreted more in monolayer. IL-8 is the most secreted molecule in both adherents and tumorspheres by all cultures.
Conclusions
Our preliminary results suggest that high levels of IL-6 and IL-8 were detected in all samples. IL-8, IL-13, IL-17A and IFN secreted by lung CSCs could be involved in the modulation of the immune microenvironment. Additionally, adherent cells show increased levels of IL-6 and TNFa compared to tumorspheres, and IL-8, IL-4, IFN, IL-10, IL-13, IL-17A show the opposite. The next is to extend the cohort to validate our results and to study others immunoregulatory factors. Supported by grants from FEDER and PI12-02838 and PI15-00753 from ISCIII.
Clinical trial identification
Legal entity responsible for the study
Fundación de Investigación del Hospital General Universitario de Valencia.
Funding
Supported by grants from FEDER and PI12-02838 and PI15-00753 from ISCIII.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2300 - AXL has a prognostic role in metastatic colorectal cancer (mCRC) and is a predictive biomarker of lack of efficacy of chemotherapy (CT) + cetuximab in RAS wild type (WT) patients (pts)
Presenter: Claudia Cardone
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
2834 - Multimodal detection of homologous recombination repair gene mutations (HRRm) in a Phase II trial of olaparib plus abiraterone in metastatic castrate resistant prostate cancer (mCRPC)
Presenter: Thomas Carr
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3596 - Identification of a highly suppressive Treg subset associated to immunotherapy response
Presenter: Emilio Giunta
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3705 - A Novel Framework for Evaluating Biomarker Response Relationships in Immuno-oncology (IO)
Presenter: Jeffrey Evelhoch
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5332 - Comparison of OncoBEAM and NGS methods to detect plasma EGFR T790M mutations at progression of NSCLC
Presenter: Jessica Garcia
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5700 - Differential expression of PD-L1 and immune biomarkers by age: Decreased expression in pediatric/AYA patients with advanced cancer
Presenter: Omid Hamid
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
966 - Potential resistance mechanisms revealed primary resistance to crizotinib in ROS1+ non-small-cell lung cancer using next generation sequencing: A multicenter study
Presenter: Quxia Zhang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
2171 - Prevalence of CLDN18.2, HER2, and PD-L1 in Gastric Cancer Samples
Presenter: Diarmuid Moran
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
2318 - Epigenetic markers in circulating cell-free DNA for detection of early stage colorectal cancer
Presenter: Yanqun Liu
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3625 - Detection and clearance of RET variants in plasma cell free DNA (cfDNA) from patients (pts) treated with LOXO-292
Presenter: Benjamin Besse
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract