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- W3205722390 abstract "PD-1/PD-L1 blockade therapeutic strategy has revolutionized the oncological treatment landscape. Patients with chemo-resistant immunogenic triple-negative breast cancer (TNBC) tumors were among the top listed applicable candidates for PD-1/PD-L1 inhibitors. Yet, TNBC patients developing innate and adaptive immune-resistance have started to appear in the clinics. Thus it became essential to identify novel predictive biomarkers to discriminate between resistant and responsive TNBC patients in a precision immune-oncological approach. Our research group is currently focusing on molecular engines controlling PD-L1 in TNBC patients and cell lines. CCAT1 long noncoding RNA and let-7a microRNA are among the recently identified regulators of PD-L1. The aim of this study was to investigate the synchronization between CCAT1 and let-7a in regulating PD-L1 in TNBC patients and cell lines. TNBC patients (n=17) were recruited into the study. MDA-MB-231 cells were cultured and transfected with let-7a mimics and CCAT1 siRNAs using HiPerFect Transfection Reagent. Total RNA was extracted using Biozol reagent, reverse transcribed and quantified using qRT-PCR. MTT and colony-forming assays were performed. TNBC patients showed a marked repression of let-7a, inversely correlated with elevated CCAT1, c-Myc and PD-L1 expression levels. Ectopic expression of let-7a and/or knockdown of CCAT1 resulted in a significant repression of PD-L1 in MDA-MB-231 cells and thus halt TNBC cellular viability and colony-forming ability. let-7a mimics resulted in a repression of c-Myc-regulated CCAT1 while CCAT1 siRNAs induced let-7a levels. Mechanistically, it was found that the impact of let-7a on CCAT1 is mediated by c-Myc. let-7a mimics resulted in repression of c-Myc and downstream CCAT1 lncRNA. This study highlights Let-7a/c-Myc/CCAT1 as a novel immunoregulatory loop for PD-L1 in TNBC patients and cell lines. Nonetheless, this study underlines the significance of let-7a and CCAT1 as novel predictive immunomodulatory biomarkers in PD-L1-overexpressing TNBC patients." @default.
- W3205722390 created "2021-10-25" @default.
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- W3205722390 date "2021-10-01" @default.
- W3205722390 modified "2023-09-26" @default.
- W3205722390 title "32P Immunoregulatory loop between let-7a and CCAT1 lncRNA coordinated by c-Myc underlies the PD-1/PD-L1 immunoresistance in triple negative breast cancer patients" @default.
- W3205722390 doi "https://doi.org/10.1016/j.annonc.2021.08.2028" @default.
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