Abstract 2167
Background
Continuous effort unraveled GPI pathway that anchors cell surface proteins mediating tumor microenvironment interactions. GPI axis is initiated in breast cancer upon PIG-C elevation which induces MSLN surface expession. MSLN is anti-apoptotic GPI-AP, whose immune therapies yielded tremendous results. CD80 is a unique immunomodulator that binds to CD28, CTLA4 and PDL1. Recombinant GPI-CD80 is evaluated as tumor vaccine. RNAi is a promising tool for immuno-targeted therapy as crucial immuno modulators are blocked. Our aim is to investigate impact of nc-RNAs on MSLN, PIG-C and CD80 for the first time.
Methods
miR-2355, miR-455 and NEAT-1 targeted MSLN, PIG-C and CD80 by bioinformatic analysis. MSLN/CD80 plasmids were transfected in MDA-MB-231 cells, then treated with synthetic nc-RNAs. Surface CD80 and MSLN were assessed by flow cytometry.Gene mRNA level was tested by q-PCR.
Results
PIG-C Silencing, NEAT-1 and miR-2355 elevation, plus NEAT-1/miR-2355 combination droped PIG-C mRNA level signtificantly (p < 0.0001 each) compared to untreated cells and miR-2355 inhibitor (P < 0.0001) miR-2355 elevation significantly droped MSLN mRNA level compared to untreated cells (P < 0.0001) Conversely, miR-2355 inhibitor, NEAT-1 mimic and NEAT-1/miR-2355 combination significantly increased MSLN expression level (P < 0.0001 each). PIG-C siRNA did not have significant effect on MSLN mRNA level PIG-C siRNA and miR-2355 mimic significantly droped MSLN surface level MFI compared to mock (P < 0.0001 each) but miR-2355 inhibitor significantly increased MSLN MFI (P < 0.0001) NEAT-1 mimic and NEAT-1/miR-2355 combination did not have significant effect on MSLN MFI. miR-455 mimic signifincantly droped both surface CD80 MFI and CD80 mRNA level compared to mock (P < 0.0001) Contrastingly, miR-455 inhibitor significantly increased both CD80 MFI and CD80 mRNA level compare to mock (P < 0.0001) NEAT-1 mimic and NEAT-1/miR-455 combination did not show significant effect on CD80 MFI or CD80 mRNA level.
Conclusions
To sum up, our study sheds light on new targets for breast cancer immunotherapy. NEAT-1 is dominant promising sponge for several mi-RNAs which potientiates its role in governing many immunomoduolatory pathways. Our study paves the way for future investigations on the role of NEAT-1 in immuno-targeted therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1885 - Factors associated with disease progression in patients treated with trametinib in combination with dabrafenib for unresectable advanced BRAFV600-mutant melanoma: an open label, non randomized study
Presenter: Philippe Saiag
Session: Poster Display session 3
Resources:
Abstract
5259 - Integrative RNAseq and Target panel sequencing reveals common and distinct innate and adaptive resistance mechanisms to BRAF inhibitors
Presenter: Phil Cheng
Session: Poster Display session 3
Resources:
Abstract
5619 - Effective treatment with T-VEC monotherapy in Stage IIIB/C-IVM1a Melanoma of the Head & Neck Region
Presenter: Viola Franke
Session: Poster Display session 3
Resources:
Abstract
5666 - Re-introduction of T-VEC Monotherapy in Recurrent Stage IIIB/C-IVM1a melanoma is effective
Presenter: Viola Franke
Session: Poster Display session 3
Resources:
Abstract
4117 - Efficacy of talimogene laherparepvec (T-VEC) in melanoma patients (pts) with locoregional (LR) recurrence, including in-transit metastases (ITM): subgroup analysis of the phase 3 OPTiM study
Presenter: Mark Middleton
Session: Poster Display session 3
Resources:
Abstract
5303 - Real Life Use of Talimogene Laherparepvec in Melanoma in Centers in Austria and Switzeland
Presenter: Christoph Hoeller
Session: Poster Display session 3
Resources:
Abstract
4130 - Outcomes of advanced melanoma patients who discontinued pembrolizumab (pembro) after complete response (CR) in the French early access program (EAP)
Presenter: Philippe Saiag
Session: Poster Display session 3
Resources:
Abstract
2050 - Outcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)
Presenter: Sarah Knispel
Session: Poster Display session 3
Resources:
Abstract
1618 - Comparative-Effectiveness of Pembrolizumab vs. Nivolumab for Patients with Metastatic Melanoma
Presenter: Justin Moser
Session: Poster Display session 3
Resources:
Abstract
3556 - Long-term efficacy of combination nivolumab and ipilimumab for first-line treatment of advanced melanoma: a network meta-analysis
Presenter: Peter Mohr
Session: Poster Display session 3
Resources:
Abstract