Abstract 44P
Background
Advancements in cancer therapy have led to improved outcomes for many breast cancer subtypes. Yet, triple-negative breast cancer (TNBC) patients continue to face significant challenges, including chemo- and immuno-resistance. Calreticulin (CALR) is a pro-phagocytic surface marker necessary for calreticulin-mediated phagocytosis. However, as part of the immune evasion tactics of the cancer cells, a deregulated expression of CALR is evidenced in several malignancies and accompanied by induced elevation of the immune suppressive CD47 on cancer cells. Yet, the CALR/CD47 expression pattern in TNBC are still controversial. Natural compounds, such as methoxylated quercetin glycoside (MQG) isolated from Cleome droserifolia, have emerged as promising therapeutic agents due to their multi-targeting approach for oncogenic and immunogenic pathways in TNBC cells. This study aims to unravel the expression pattern of CALR/CD47 in TNBC patients and to investigate the modulatory role of MQG on the CALR/CD47 axis in MDA-MB-231.
Methods
Breast cancer (BC) patients were recruited. All clinical data of patients were collected. MDA-MB-231 cells were cultured and treated with MQG or vehicle control. Total RNA was extracted from breast tissues and cell lines. RNA concentration and quality were assessed using nanodrop. One-step qPCR was performed to determine the expression level of CALR and CD-47.
Results
CALR/CD-47 were upregulated in BC tissues compared to their normal counterparts and significantly higher in TNBC patients compared to non-TNBC patients. Furthermore, CALR/CD-47 overexpression were significantly correlated with the aggressiveness of tumors implicated in lymph node metastasis and pre-menopausal onset. MDA-MB-231 cells treated with MQG significantly reduced CALR while induced the immune suppressor CD-47 in treated cells compared to vehicle control cells.
Conclusions
Deregulated immune checkpoint CALR/CD47 expression in TNBC patients correlates with disease aggressiveness. This study suggests harnessing TNBC immunotherapeutic resistance through a combinational approach and targeted therapeutic modality, including MQG and CD-47 antibodies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Instutional Research Grant-American University in Cairo.
Disclosure
All authors have declared no conflicts of interest.