Rabani S., Gunes E. G., Gunes M., Pellegrino B., Lampert B., David K., Pillai R., Li A., Becker-Herman S., Rosen S. T. & Shachar I.
(2024)
Cell Reports.
43,
11,
114920.
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. The tumor microenvironment (TME) plays a major regulatory role in TNBC progression and is highly infiltrated by suppressive immune cells that reduce anti-tumor immune activity. Although regulatory B cells (Bregs) are a key TME component, knowledge of their function in TNBC is limited. CD84 is a homophilic adhesion molecule that promotes the survival of blood tumors. In the current study, we followed the role of CD84 in the regulation of the TME in TNBC. We demonstrate that CD84 induces a cascade in Bregs that involves the β-catenin and Tcf4 pathway, which induces the transcription of interleukin-10 by binding to its promoter and the promoter of its regulator, AhR. This leads to the expansion of Bregs, which in turn control the activity of other immune cells and immune suppression. Accordingly, we suggest CD84 as a therapeutic target for breaking immune tolerance in TNBC.
Gunes M., Rosen S. T., Shachar I. & Gunes E. G.
(2024)
Frontiers in Immunology.
15,
1297473.
Recently, cancer immunotherapy has revolutionized cancer treatment. Various forms of immunotherapy have a manageable safety profile and result in prolongation of overall survival in patients with solid tumors, but only in a proportion of patients. Various factors in the tumor microenvironment play critical roles and may be responsible for this lack of therapeutic response. Signaling lymphocytic activation molecule family (SLAMF) members are increasingly being studied as factors impacting the tumor immune microenvironment. SLAMF members consist of nine receptors mainly expressed in immune cells. However, SLAMF receptors have also been detected in cancer cells, and they may be involved in a spectrum of anti-tumor immune responses. Here, we review the current knowledge of the expression of SLAMF receptors in solid tumors and tumor-infiltrating immune cells and their association with patient outcomes. Furthermore, we discuss the therapeutic potential of targeting SLAMF receptors to improve outcomes of cancer therapy in solid tumors. We believe the research on SLAMF receptor-targeted strategies may enhance anti-cancer immunity in patients with solid tumors and improve clinical outcomes.
Lewinsky H., Gunes E. G., David K., Radomir L., Kramer M. P., Pellegrino B., Perpinial M., Chen J., He T. F., Mansour A. G., Teng K. Y., Bhattacharya S., Caserta E., Troadec E., Lee P., Feng M., Keats J., Krishnan A., Rosenzweig M., Yu J., Caligiuri M. A., Cohen Y., Shevetz O., Becker-Herman S., Pichiorri F., Rosen S. & Shachar I.
(2023)
JCI insight.
8,
14,
The authors recently became aware of inadvertent errors in Figure 1F. In the original version, the representative flow plots provided for CD14 HD-PD and CD14+ HD-PD were incorrect.
