ABSTRACT
Liquid biopsy, specifically circulating tumor DNA (ctDNA) detection, has started to revolutionize the clinical management of patients with cancer by surpassing many limitations of traditional tissue biopsies, particularly for serial testing. ctDNA sequencing has been successfully utilized for cancer detection, prognostication, and assessment of disease response and evolution. While the applications of ctDNA analysis are growing, the majority of studies to date have primarily evaluated its use as a tool for tracking a known cancer, and in most cases at advanced stage. Herein, we discuss the potential application of ctDNA for surveillance and early cancer detection in patients with a cancer predisposition syndrome.
Subject(s)
Biomarkers, Tumor/genetics , Circulating Tumor DNA/genetics , Early Detection of Cancer/methods , Genetic Predisposition to Disease , Genetic Testing/methods , Neoplastic Cells, Circulating/pathology , Neoplastic Syndromes, Hereditary/diagnosis , Circulating Tumor DNA/blood , Humans , Neoplastic Cells, Circulating/metabolism , Neoplastic Syndromes, Hereditary/blood , Neoplastic Syndromes, Hereditary/genetics , PrognosisABSTRACT
The B7 family plays a critical role in both positive and negative regulation of immune responses by engaging a variety of receptors on lymphocytes. Importantly, blocking coinhibitory molecules using antibodies specific for CTLA-4 and PD-1 enhances tumor immunity in a subset of patients. Therefore, it is critical to understand the role of different B7 family members since they may be suitable therapeutic targets. B7-H4 is another member that inhibits T-cell function, and it is also upregulated on a variety of tumors and has been proposed to promote tumor growth. Here, we investigate the role of B7-H4 in tumor development and show that B7-H4 expression inhibits tumor growth in two mouse models. Furthermore, we show that B7-H4 expression is required for antitumor immune responses in a mouse model of mammary tumorigenesis. We found that the expression levels of B7-H4 correlate with MHC class I expression in both mouse and human samples. We show that IFNγ upregulates B7-H4 expression on mouse embryo fibroblasts and that the upregulation of B7-H4 on tumors is dependent on T cells. Notably, patients with breast cancer with increased B7-H4 expression show a prolonged time to recurrence. These studies demonstrate a positive role for B7-H4 in promoting antitumor immunity.