Pan-Cancer Analysis of Ligand-Receptor Cross-talk in the Tumor Microenvironment.

Signaling between cancer and nonmalignant (stromal) cells in the tumor microenvironment (TME) is a key to tumor progression. Here, we deconvoluted bulk tumor transcriptomes to infer cross-talk between ligands and receptors on cancer and stromal cells in the TME of 20 solid tumor types. This approach recovered known transcriptional hallmarks of cancer and stromal cells and was concordant with single-cell, in situ hybridization and IHC data. Inferred autocrine cancer cell interactions varied between tissues but often converged on Ephrin, BMP, and FGFR-signaling pathways. Analysis of immune checkpoints nominated interactions with high levels of cancer-to-immune cross-talk across distinct tumor types. Strikingly, PD-L1 was found to be highly expressed in stromal rather than cancer cells. Overall, our study presents a new resource for hypothesis generation and exploration of cross-talk in the TME. SIGNIFICANCE: This study provides deconvoluted bulk tumor transcriptomes across multiple cancer types to infer cross-talk in the tumor microenvironment.

Randomized controlled trial of mechanical bowel preparation for laparoscopy-assisted colectomy.

INTRODUCTION: The benefit of mechanical bowel preparation (MBP) before open colon surgery has been debated over the last decade. The aim of this randomized controlled trial was to evaluate the effect of MBP on the outcome of patients who underwent elective laparoscopic colectomy. METHODS: Patients who were scheduled to undergo elective laparoscopic colon resection with primary anastomosis were randomly allocated to a preoperative MBP group (either two bottles of sodium phosphate or 2-L polyethylene glycol) or a no-MBP group. Anastomotic leakage and other complications such as surgical-site infection and extra-abdominal complications were recorded postoperatively. RESULTS: In this study, 122 patients were recruited and randomly allocated to the MBP group (n = 62) or the no-MBP group (n = 60). Demographic and clinical characteristics were not significantly different between the two groups. The rate of abdominal complications, including anastomotic leak and surgical-site infection, was 16.2% in the MBP group and 18.3% in the no-MBP group (P = 0.747). Anastomotic leakage occurred in four patients (6.5%) in the MBP group and in two patients (3.3%) in no-MBP group (P = 0.680). About 29% of patients in the MBP group still had either liquid or solid content in the bowel. No significant difference was found between the length of hospital stay in the MBP group and the no-MBP group (9.0 ± 2.9 vs 8.4 ± 1.9 days, P = 0.180). CONCLUSIONS: Elective laparoscopic colectomy without MBP is safe and offers acceptable postoperative morbidity.

Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Modify Microglial Response and Improve Clinical Outcomes in Experimental Spinal Cord Injury.

No current clinical intervention can alter the course of acute spinal cord injury (SCI), or appreciably improve neurological outcome. Mesenchymal stromal cells (MSCs) have been shown to modulate the injury sequelae of SCI largely via paracrine effects, although the mechanisms remain incompletely understood. One potential modality is through secretion of extracellular vesicles (EVs). In this study, we investigate whether systemic administration of EVs isolated from human MSCs (MSCEv) has the potential to be efficacious as an alternative to cell-based therapy for SCI. Additionally, we investigate whether EVs isolated from human MSCs stimulated with pro-inflammatory cytokines have enhanced anti-inflammatory effects when administered after SCI. Immunohistochemistry supported the quantitative analysis, demonstrating a diminished inflammatory response with apparent astrocyte and microglia disorganization in cord tissue up to 10 mm caudal to the injury site. Locomotor recovery scores showed significant improvement among animals treated with MSCEv. Significant increases in mechanical sensitivity threshold were observed in animals treated with EVs from either naïve MSC (MSCEvwt) or stimulated MSC (MSCEv+), with a statistically significant increase in threshold for MSCEv+-treated animals when compared to those that received MSCEvwt. In conclusion, these data show that treatment of acute SCI with extracellular vesicles derived from human MSCs attenuates neuroinflammation and improves functional recovery.