Tumor immune infiltration estimated from gene expression profiles predicts colorectal cancer relapse

A substantial fraction of patients with stage I-III colorectal adenocarcinoma (CRC) experience disease relapse after surgery with curative intent. However, biomarkers for predicting the likelihood of CRC relapse have not been fully explored. Therefore, we assessed the association between tumor infiltration by a broad array of innate and adaptive immune cell types and CRC relapse risk. We implemented a discovery-validation design including a discovery dataset from Moffitt Cancer Center (MCC; Tampa, FL) and three independent validation datasets: (1) GSE41258 (2) the Molecular Epidemiology of Colorectal Cancer (MECC) study, and (3) GSE39582. Infiltration by 22 immune cell types was inferred from tumor gene expression data, and the association between immune infiltration by each cell type and relapse-free survival was assessed using Cox proportional hazards regression. Within each of the four independent cohorts, CD4+ memory activated T cell (HR: 0.93, 95% CI: 0.90-0.96; FDR = 0.0001) infiltration was associated with longer time to disease relapse, independent of stage, microsatellite instability, and adjuvant therapy. Based on our meta-analysis across the four datasets, 10 innate and adaptive immune cell types associated with disease relapse of which 2 were internally validated using multiplex immunofluorescence. Moreover, immune cell type infiltration was a better predictors of disease relapse than Consensus Molecular Subtype (CMS) and other expression-based biomarkers (Immune-AICMCC:238.1-238.9; CMS-AICMCC: 241.0). These data suggest that transcriptome-derived immune profiles are prognostic indicators of CRC relapse and quantification of both innate and adaptive immune cell types may serve as candidate biomarkers for predicting prognosis and guiding frequency and modality of disease surveillance

Decrease in the Size of Fat-Enlarged Axillary Lymph Nodes and Serum Lipids after Bariatric Surgery

Background: Ectopic fat deposition in obesity is associated with organ dysfunction; however, little is known about fat deposition within the lymphatic system and associated lymphatic dysfunction. Methods: One hundred fifty-five women who underwent routine screening mammography before and after a Roux-en-y gastric bypass or a sleeve gastrectomy were retrospectively reviewed and after excluding women without visible nodes both before and after bariatric surgery, 84 patients were included in the final analysis. Axillary lymph node size, patient weight in kilograms, body mass index, and a diagnosis of hypertension, type 2 diabetes, and dyslipidemia were evaluated before and after surgery. Binary linear regression models and Fischer’s exact test were used to evaluate the relationship between the size of fat-infiltrated axillary lymph nodes, patient age, change in patient weight, and diagnosis of hypertension, type 2 diabetes, and dyslipidemia. Results: Fat-infiltrated axillary lymph nodes demonstrated a statistically significant decrease in size after bariatric surgery with a mean decrease of 4.23 mm (95% CI: 3.23 to 5.2, p < 0.001). The resolution of dyslipidemia was associated with a decrease in lymph node size independent of weight loss (p = 0.006). Conclusions: Mammographically visualized fat-infiltrated axillary lymph nodes demonstrated a statistically significant decrease in size after bariatric surgery. The decrease in lymph node size was significantly associated with the resolution of dyslipidemia, independent of weight loss, age, and type of surgery