Triple Negative Breast Cancer
- Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype. The tumor microenvironment (TME) plays a major regulatory role in TNBC progression. Regulatory B cells (Bregs) are immune suppressive B cells that inhibit antitumor immune activity, thereby advancing tumor growth. CD84 (SLAMF5) is a homophilic adhesion molecule that promotes the survival of blood tumors including chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). In this study we follow the role of CD84 in the regulation of the TME and specifically Bregs in TNBC.
- CD74 is a cell-surface receptor for the cytokine macrophage migration inhibitory factor (MIF). MIF binding to CD74 induces a signaling cascade resulting in the release of its cytosolic intracellular domain (CD74-ICD), which regulates transcription in naive B and chronic lymphocytic leukemia (CLL) cells. Currently we investigate the role of CD74 in the regulation of the TME in TNBC. The tumor and immune cells in TNBC express high levels of CD74; however, the function of this receptor in the tumor environment has not been extensively characterized. Regulatory B cells (Bregs) and tolerogenic dendritic cells (tol-DCs) were previously shown to attenuate the antitumor immune response in TNBC. Our current results suggest that CD74+ CD11c+ DCs are the dominant cell type involved in the regulation of TNBC progression. These findings indicate that CD74 might serve as a novel therapeutic target in triple-negative breast cancer.
Glioblastoma
- Glioblastoma (GBM), a grade IV astrocytoma, is one of the most aggressive forms of primary brain cancer, marked by rapid cell growth, significant cellular diversity, and resistance to treatments. Despite medical advancements, GBM has a poor prognosis, with a median survival time of only 12–18 months and just 5% of patients surviving beyond five years. The tumor’s highly immunosuppressive microenvironment (TME) plays a crucial role in its resistance to standard therapies and its ability to evade the immune system. Investigating the TME is vital for uncovering the mechanisms that drive immune tolerance. Gaining insight into these interactions could lead to new therapeutic strategies aimed at reprogramming the TME and boosting anti-tumor immune responses. Overcoming this immune tolerance through innovative treatments could potentially improve patient outcomes.
- In our current study we aim to unveil if SLAMF5 regulates immune tolerance in GBM, as observed in TNBC, through its expression on myeloid cells, as seen in MS. By inhibiting SLAMF5, we anticipate that the tumor microenvironment (TME) will shift to a pro-inflammatory state, thereby reducing tumor burden. The goal of this study is to investigate the role of SLAMF5 in the TME by blocking its expression in a murine GBM model. While our primary focus is on myeloid cells, we will also examine other immune cell types, including T and B cells. Additionally, we plan to explore the molecular mechanisms through which SLAMF5 influences the TME in GBM.