Abstract 175P
Background
Cancer cells evade the human immune system by manipulating the tumor-immune microenvironment (TIME) via suppressing the immuno-activator and promoting the immune-suppressive mediators. Hence, targeting immuno-modulatory factors became an ingenious treatment option, particularly for cancer types that shows scarcity of treatment options such as triple negative breast cancer (TNBC). Novel immuno-modulatory targets such as Galectin (GAL) 3 and 9 have been found to be overexpressed in TNBC, repressing the immune surveillance. Similarly, TNBC tumors were found to prevent the activation of immune infiltrating lymphocytes via overexpressing immune checkpoint CD155 expression on its surface. MHC class I polypeptide–related sequence A (MICA) and MICB are stress-induced ligands essential for innate immunity activation at the TIME. However, their expression is also often suppressed in TNBC, leading to immune suppression and poor prognosis. Our research group has extensively worked on microRNAs to modulate multiple targets simultaneously. Hence, this work unravels the expression profile of the miR-548c in BC tissues, evaluate its unprecedented immunomodulatory role in TNBC via altering GAL3/9, CD155, and MICA/B expression.
Methods
BC female patients (n=20) were recruited. In-silico analysis was used to identify miRNAs that target immunomodulatory targets. MDA-MB-231 TNBC cells were cultured and transfected by oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR.
Results
miRNA-548c is a down-regulated tumor suppressor miRNA in BC tissues compared to its normal counterparts. MiRNA-548c was validated to regulate the immunogenic profile in TNBC. Given the overexpression of the immuno-suppressive GAL3, GAL9, and CD155, miR-548c simultaneously constrained their expression in TNBC cells. Moreover, ectopic expression of miR-548c in MDA-MB-231 cells resulted in a marked upregulation of the expression of the immuno-activators MICA and MICB, enhancing the overall immunogenic profile of TNBC cells.
Conclusions
This study identifies miRNA-548c as a booster of the immune surveillance by concomitant adjustment for the immunogenic ligands expressed/produced by the TNBC cell.
Legal entity responsible for the study
The authors.
Funding
This work was supported by Swiss National Science Foundation (SNSF), grant IZSTZ0_198887.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
14P - Integrated modelling of T cell repertoires to identify clonotype signatures of ICI response
Presenter: Juan Luis Melero
Session: Poster Display
16P - Exosomal PD-L1 and lactate predict clinical outcomes of PD-1 blockade combined with chemotherapy in advanced-stage gastric and gastroesophageal junction adenocarcinoma
Presenter: Yongshun Chen
Session: Poster Display
17P - Spatial Characteristics Associated with the Chemo and Immuno-treatment Response of Gastric Cancer Revealed by Multi-omics Analysis
Presenter: Gang Che
Session: Poster Display
18P - Association of DNA methylation profiles with pathologic complete response in early triple negative breast cancer patients receiving neoadjuvant chemoimmunotherapy
Presenter: Angelika Starzer
Session: Poster Display
19P - The prognostic value of soluble CD73 in advanced triple-negative breast cancer: an exploratory analysis of the SYNERGY trial
Presenter: Denis Zoë
Session: Poster Display
21P - Mass cytometry reveals a population of exhausted CD8+ T cells associated with durvalumab/tremelimumab/vinorelbine efficacy in advanced cervical cancer (iMOVIE).
Presenter: Alexandre Bertucci
Session: Poster Display
22P - Predictive value of Tertiary Lymphoid Structure in patients with mismatch repair deficient advanced/ recurrent endometrial cancer treated with Dostarlimab.
Presenter: Maria Kfoury
Session: Poster Display
23P - Circulating immune cells and activity of immune checkpoint inhibitors in metastatic renal cell carcinoma
Presenter: Ronan Flippot
Session: Poster Display
24P - Chromosome 3p-related gene alterations (GA) as biomarkers for immunocombinations in metastatic renal cell carcinoma (mRCC): a hypothesis-generating analysis
Presenter: Matteo Rosellini
Session: Poster Display