Tspan6 stimulates the chemoattractive potential of breast cancer cells for B cells in an EV- and LXR-dependent manner.

The immune microenvironment in breast cancer (BCa) is controlled by a complex network of communication between various cell types. Here, we find that recruitment of B lymphocytes to BCa tissues is controlled via mechanisms associated with cancer cell-derived extracellular vesicles (CCD-EVs). Gene expression profiling identifies the Liver X receptor (LXR)-dependent transcriptional network as a key pathway that controls both CCD-EVs-induced migration of B cells and accumulation of B cells in BCa tissues. The increased accumulation oxysterol ligands for LXR (i.e., 25-hydroxycholesterol and 27-hydroxycholesterol) in CCD-EVs is regulated by the tetraspanin 6 (Tspan6). Tspan6 stimulates the chemoattractive potential of BCa cells for B cells in an EV- and LXR-dependent manner. These results demonstrate that tetraspanins control intercellular trafficking of oxysterols via CCD-EVs. Furthermore, tetraspanin-dependent changes in the oxysterol composition of CCD-EVs and the LXR signaling axis play a key role in specific changes in the tumor immune microenvironment.

Characterization of the Immune Microenvironment in Inflammatory Breast Cancer Using Multiplex Immunofluorescence.

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. METHODS: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. RESULTS: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. CONCLUSION: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

Antibiotic Prophylaxis in Adults With Open Tibial Fractures: What Is the Evidence for Duration of Administration? A Systematic Review.

Open tibial fractures are common injuries after high-energy trauma such as road traffic accidents. Infection is one of the main complications of open fractures. Broad-spectrum antibiotics have been used for prophylaxis and treatment of infection in these fractures. The duration of antibiotic prophylaxis remains controversial, especially for the different types and grades of open fractures. No complete review, to date, has been performed of published studies to demonstrate the wide variety of duration of antibiotic use in practice to prevent infection, especially in open tibial fractures. The purpose of the present study was to review the evidence in the current data regarding the duration of prophylactic antibiotic administration in open tibial fractures and to identify the optimum duration of administration of antibiotics to minimize the risk of infection in these fractures. We reviewed and evaluated all published clinical trials claiming or cited elsewhere as being authoritative regarding the duration of prophylactic antibiotic use in open tibial fracture management. A large number of studies reported antibiotic prophylaxis in open fractures; however, only 8 met the inclusion criteria set out for our review. Only 1 randomized, double-blind, prospective study examined the duration of prophylactic antibiotic administration in open tibial fractures. That study suggested a short course of antibiotics is as effective as a long course in infection prophylaxis. The results of the present review highlight the need for a rigorous randomized, double-blind, multicenter trial to establish an agreed protocol for the optimal length of prophylactic antibiotic administration in open tibial fractures.