Immune Checkpoint and EMT-Related Molecules in Circulating Tumor Cells (CTCs) from Triple Negative Breast Cancer Patients and Their Clinical Impact

Abstract

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. There are few targeted therapies for these patients, leading to an unmet need for new biomarkers. The present study aimed to investigate the expression of PD-L1, CTLA-4, GLU, and VIM in CTCs of TNBC patients. Ninety-five patients were enrolled in this study: sixty-four TNBC and thirty-one luminal. Of these patients, 60 were in the early stage, while 35 had metastatic disease. Protein expression was identified by immunofluorescence staining experiments and VyCAP analysis. All the examined proteins were upregulated in TNBC patients. The expression of the GLU+VIM+CK+ phenotype was higher (50%) in metastatic TNBC compared to early TNBC patients (17%) (p = 0.005). Among all the BC patients, a significant correlation was found between PD-L1+CD45−CK+ and CTLA-4+CD45−CK+ phenotypes (Spearman test, p = 0.024), implying an important role of dual inhibition in BC. Finally, the phenotypes GLU+VIM+CK+ and PD-L1+CD45−CK+ were associated with shorter OS in TNBC patients (OS: log-rank p = 0.048, HR = 2.9, OS: log-rank p < 0.001, HR = 8.7, respectively). Thus, PD-L1, CTLA-4, GLU, and VIM constitute significant biomarkers in TNBC associated with patients’ outcome, providing new therapeutic targets for this difficult breast cancer subtype.

Comprehensive Analysis of CXCR4, JUNB, and PD-L1 Expression in Circulating Tumor Cells (CTCs) from Prostate Cancer Patients

“…Furthermore, morphological characteristics of CTCs described by Adam et al and Park et al were observed in subpopulations of CTCs detected in the present study [33,34]. According to the CTC morphology observed on the (CK/PD-L1/CD45) staining, a second slide from each patient was analyzed for the assessment of CXCR4 and JUNB expression in CTCs, using antibodies against CK, CXCR4, and JUNB (CK/CXCR4/JUNB), as we have previously reported [19,30].…”

“…In patients, PD-L1 is expressed in cancer cells and inhibits the cytotoxic effect of CD8+ T cells against them [3,16]. Several studies have shown increased PD-L1 protein expression in CTCs of different cancer types, including prostate cancer, which is potentially related to patient outcomes [15][16][17][18][19]. Furthermore, the evolution of molecular assays for the detection of PD-L1 mRNA expression has shown that the detection of PD-L1 expression in CTCs is practicable and can provide real-time clinical information [20].…”

Molecular and serological biomarkers to predict trastuzumab responsiveness in HER-2 positive breast cancer

“…Breast cancer is the most common form of malignancy affecting Iraqi women, accounting for one-third of all cancers [ 21 , 22 ]. HER-2-positive breast cancers account for more than twenty percent of cases and have a high rate of disease recurrence and mortality [ 23 ]. Given the increasing incidence of breast cancer and HER-2 mutation, identifying new biomarkers to correlate with therapeutic response is crucial.…”

Role of KDM2B epigenetic factor in regulating calcium signaling in prostate cancer cells

“…Finally, cells were mounted on an anti-fade reagent containing 4′,6-diamidino-2-phenylindole (DAPI). Subsequently, samples were examined using VyCAP (VyCAP B.V., Enschede, the Netherlands) ( Roumeliotou et al, 2022 , Vardas et al, 2023 ).…”