Search

Breast cancer is one of the most threatening women health diseases worldwide and its molecular heterogeneity offers a range of response to therapy. The role of polyamine metabolism is receiving increasing attention. Polyamine metabolism not only plays an important role in the occurrence and development of breast cancer, but also interacts with tumor immune microenvironment. In this work, we applied single-cell RNA-sequencing (scRNA-seq) and systems immunological approaches to interrogate immune cell infiltration gene-to-gene co-expressions in the bulk tumor transcriptomes of breast cancer. We acquired breast cancer sample data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), evaluated the infiltration status of 22 immune cell types using CIBERSORTx tool, respectively. By leveraging the Retrospective Breast sample of various technologies including gene expression and methylation, we identified 46 breast cancer proliferation-associated co-expression modules using weighted gene coexpression network analysis (WGCNA) approach along with machine learning models which in turn delineated single cell level expressions features that these selected module possessed. We observed substantial cellular heterogeneity in the breast cancer microenvironment, where lineage-specific gene expression patterns were highly associated with tumor progression. Moreover, we also identified the gene modules correlated with immune cell infiltration level that could function as regulators in response to tumors for immune therapy. Moreover, risk scores were correlated with immune cell function in different patient groups defined by high- and low-risk. The findings of this study shed a new light upon molecular classification prognostic assessment and personalized treatment in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Periodontal disease (PerioD) is a chronic, complex inflammatory condition resulting from the interaction between subgingival dysbiotic bacteria and the host immune response leading to local inflammation. Since periodontal inflammation is characterized by multiple cytokines effects we investigated whether Periodontal Inflamed Surface Area (PISA), a continuous measure of clinical periodontal inflammation is a predictor of composite indexes of salivary cytokines. Methods and findings: In a cross-sectional study of 67 healthy, well-educated individuals, we evaluated PISA and several cytokines expressed in whole stimulated saliva. Two salivary cytokine indexes were constructed using weighted and unweighted approaches based on a Principal Component Analysis [named Cytokine Component Index (CCI)] or averaging the (standardized) level of all cytokines [named Composite Inflammatory Index (CII)]. In regression analysis we found that PISA scores were significantly associated with both salivary cytokine constructs, (CCI: part R = 0.51, p<0.001; CII: part R = 0.40, p = 0.001) independent of age, gender and BMI showing that single scores summarizing salivary cytokines correlated with severity of clinical periodontal inflammation. Conclusions: Clinical periodontal inflammation may be reflected by a single score encompassing several salivary cytokines. These results are consistent with the complexity of interactions characterizing periodontal disease. In addition, Type I error is likely to be avoided. [ABSTRACT FROM AUTHOR]

The discovery of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, together with an improved insight in dendritic cell biology illustrating their key function in the immune system, have provided a rationale to initiate dendritic cell-based cancer immunotherapy trials. Nevertheless, dendritic cell vaccination is in an early stage, as methods for preparing tumor antigen presenting dendritic cells and improving their immunostimulatory function are continuously being optimized. In addition, recent improvements in immunomonitoring have emphasized the need for careful design of this part of the trials. Still, valuable proofs-of-principle have been obtained, which favor the use of dendritic cells in subsequent, more standardized clinical trials. Here, we review the recent developments in clinical DC generation, antigen loading methods and immunomonitoring approaches for DC-based trials. [ABSTRACT FROM AUTHOR]