42P - Differential expression of PD-L1, MALAT1 and XIST in tumors and lymph nodes of TNBC and IDC patients and their regulation by miR-182. (42P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Drug Development
Basic Science
Presenter Amany Samir
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors A. Samir1, R. Abdel Tawab2, H.M. El Tayebi1
  • 1Genetic Pharmacology Research Group, Department Of Pharmacology And Toxicology, German University in Cairo, 11835 - Cairo/EG
  • 2Emeritus General Surgery, Ain Shams University, 11566 - Cairo/EG

Abstract

Background

Blockade of immune checkpoint Programmed cell death protein-1, PD-1/PD-L1 became a principle approach in cancer therapy. MicroRNAs(miR) and Long-noncoding RNAs(LncRNAs) were described to have a critical role in carcinogenesis but not extensively studied in cancer immunotherapy. Our previous data revealed that overexpression of LncRNA X inactive–specific transcript(XIST) downregulates PDL-1 in breast cancer (BC). The study aims to investigate the impact of miR-182 on PD-L1 and to analyze the differential expression of PD-L1 and non coding RNAs in different BC subtypes.

Methods

BC as well as lymph node (LN) biopsies were collected from 21 BC patients (60% Triple negative(TNBC) and 40% Invasive Ductal Carcinoma(IDC)). Expression profiling of PDL-1, MALAT-1, XIST and miR-182 was quantified by Taqman Real Time qPCR and normalized by Beta-2-microglobulin and RNU6B. Manipulation of miR-182 was performed in MDA-MB-231 cells followed by quantifying the target genes by RT-qPCR.

Results

MiR-182, MALAT-1 and XIST were selected as regulators for PD-L1. The relative expression of miR-182, PD-L1 and MALAT-1 were markedly increased in all BC than controls (P = 0.0172, P = 0.0237 and P = 0.0255). MiR-182, PD-L1 and MALAT-1 expression was positively correlated (p = 0.026, p = 0.033 and p = 0.031) and higher in TNBC by 15, 7 and 79.5 folds, respectively, than IDC. However, XIST expression was inversely correlated to miR-182, PD-L1 and MALAT-1 (p = 0.043, p = 0.041 and p = 0.035) and lower in TNBC by 10 folds than IDC. Unexpectedly, PDL-1 was undetectable in IDC LNs, however, it was markedly overexpressed in TNBC LNs compared to control-LN (P = 0.0065). MALAT and XIST expression in LN was non-significant. Overexpression of miR-182 in MDA-MB-231 cells resulted in significant increase in PD-L1 and MALAT-1 expression (P = 0.0057 and P = 0.0468, respectively) and dramatic decrease in XIST (P = 0.0351). Anti-miR-182 reversed the effect of the mimics.

Conclusions

This study sheds the light on the differential expression of miR-182, MALAT-1 and XIST with a significant correlation to PD-L1 in TNBC and IDC. The data suggests a crucial role for these genes in the extent of evasion of cancer immunity in different BC subtypes.

Clinical trial identification

Legal entity responsible for the study

German University in Cairo, Egypt

Funding

None

Disclosure

All authors have declared no conflicts of interest.