Abstract 3349
Background
TNBC is the most immunogenic tumor compared to other BC subtypes. Thus, clinicians shifted the treatment among TNBC patients to immunotherapeutic alternatives such as immune checkpoint inhibitors (ICB). Despite the success of ICB, resistance in some TNBC cases had recently appeared. Thus, adding a new factor in the immunotherpeutic equation which could be the tumor microenvironment (TME); TME includes an array of immune-modulatory cytokines such as Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) that acts as a barrier in eradicating the tumor cells by the cytotoxic immune cells. Recently, our group has reported a novel crosstalk between non-coding RNAs (ncRNAs). MALAT1, an oncogenic long ncRNA, is recently reported to directly bind to microRNA-17-92 cluster. However, miR-17-5p role in TNBC is still controversial. Moreover, the impact of miR-17-5p, MALAT1 and their interplay in the TME has never been investigated. The aim of this study is to investigate the crosstalk between ncRNAs and their impact on cytokines in TME of TNBC cells.
Methods
Twenty BC patients were recruited. Bioinformatic analysis was performed using more than 5 softwares. MDA-MB-231 cells were cultured and transfected with miR-17-5p oligonucleotides. Total RNA was extracted and quantified by qRT-PCR. Cellular viability and Colony forming ability were measured using MTT and colony forming assay.
Results
MALAT-1, miR-17-5p and IL-10 were down-regulated while TNF-α was upregulated in BC tissues compared to its counterparts. In-silico analysis showed that miR-17-5p binds to MALAT-1, IL-10 and TNF-α. Experimentally, ectopic expression of miR-17-5p (>5000 folds) resulted in a marked reduction in cellular viability and colony forming ability of TNBC cells. On top of that, miR-17-5p mimics resulted in a significant repression of MALAT1. Consequently, a marked increase in IL-10 and TNF-α levels was shown. While anti-miR-17-5p resulted in a marked repression of IL-10 and TNF-α.
Conclusions
miR-17-5p is an upstream orchestrator of MALAT-1/IL-10/TNF-α shaping the TME in TNBC patients. Therefore, this study provides a novel combination therapeutic approach of Anti-miR-17-5p and ICB with decreased chance of resistance in TNBC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
German University in Cairo.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1285 - Preliminary results of STELLAR-001, a dose escalation phase I study of the anti-C5aR, IPH5401, in combination with durvalumab in advanced solid tumors.
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
3808 - GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
Presenter: Pierpaolo Correale
Session: Poster Display session 3
Resources:
Abstract
5677 - Immune correlates in peripheral blood samples in a preoperative window of opportunity randomized trial of nivolumab with or without tadalafil in resectable squamous cell carcinoma of the head and neck (SCCHN)
Presenter: Larry Harshyne
Session: Poster Display session 3
Resources:
Abstract
4854 - Phase 1 evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced malignancies
Presenter: John Powderly
Session: Poster Display session 3
Resources:
Abstract
4344 - Phase 1 Trial of CV301 in Combination with Anti-PD-1 Therapy in Non-squamous NSCLC
Presenter: Arun Rajan
Session: Poster Display session 3
Resources:
Abstract
4555 - Safety and efficacy results of the combination of DPX-Survivac, pembrolizumab and intermittent low dose cyclophosphamide (CPA) in subjects with advanced and metastatic solid tumors: preliminary results from the hepatocellular carcinoma (HCC), NSCLC, bladder cancer, & MSI-H cohorts
Presenter: Henry Conter
Session: Poster Display session 3
Resources:
Abstract
3012 - Excellent CBR and Prolonged PFS in Non-Squamous NSCLC with Oral CA-170, an Inhibitor of VISTA and PD-L1
Presenter: Vivek Radhakrishnan
Session: Poster Display session 3
Resources:
Abstract
2536 - Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers
Presenter: Christophe Le Tourneau
Session: Poster Display session 3
Resources:
Abstract
1845 - Induction of tumor-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410
Presenter: Takashi Kojima
Session: Poster Display session 3
Resources:
Abstract
5043 - Comprehensive results of a Phase Ib study with a HER2/neu B-cell peptide vaccine administered with cisplatin and 5-fluorouracil or capecitabine chemotherapy show safety, immunogenicity and clinical response in patients with HER2/Neu overexpressing advanced gastric cancer
Presenter: Ursula Wiedermann
Session: Poster Display session 3
Resources:
Abstract