Human papillomavirus (HPV) is an etiological risk factor for a subset of head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC is significant more radiosensitive than HPV-HNSCC, but the underlying mechanism is still unknown. Tumor microenvironment can affect tumor response to radiation therapy. Cancer secreted exosomes are emerging as crosstalk mediators between tumor cells and the tumor microenvironment. The main objectives of this study were to determine the role of HPV+ HNSCC-derived exosomes in increased radiation sensitivity. Here, we found that exosomes derived from HPV+ HNSCC cells activate macrophages into the M1 phenotype, which then increases the radiosensitivity of HNSCC cells. miR-9 was enriched in exosomes released from HPV+ HNSCC cells and it could be transported to macrophages, leading to altered cellular functions. Overexpression of miR-9 in macrophages induced polarization into the M1 phenotype via downregulation of PPARδ. Increased radiosensitivity was observed for HNSCC cells co-cultured with macrophages in which miR-9 was upregulated or treated with M1 macrophages. These observations suggest that HPV+ HNSCC cells secrete miR-9-rich exosomes, which then polarize macrophages into M1 phenotype and lead to increased radiosensitivity of HNSCC cells. Hence, miR-9 may be a potential treatment strategy for HNSCC..
Laryngeal squamous cell carcinoma (LSCC) is a highly malignant tumor originated from respiratory system. Although there have been many improvements in therapy until now, reducing the high mortality remains difficult. Understanding the cellular heterogeneity of LSCC could contribute to improve this problem. Single-cell RNA sequencing was applied to dissect the cell composition and molecular characteristics of LSCC tissues. Immunohistochemistry staining of the LSCC tissues was performed to identify the spatial location of tumor cells. Survival analysis of marker genes was executed in The Cancer Genome Atlas to verify the correlation between each cell clusters and patients' prognosis. The LSCC tissue cells were finely grouped into various clusters, including tumor cells, immune cells, epithelial cells, fibroblasts and endothelial cells. Notably, in tumor cells, keratinocyte-like cells were in the core of tumor while malignant proliferating cells were located at the tumor edge. The malignant proliferating cells were correlated with poor prognosis. In summary, this is the first study to delineate a landscape of the LSCC intratumor heterogeneity. Our work might help researchers have a better understanding for tumor progression.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. In addition to tobacco and alcohol, human papillomavirus (HPV) has been shown to be another important risk factor for subsets of HNSCC. 1 Interestingly, HPV + HNSCC carries a more favorable prognosis and better curative effect following radiotherapy compared with HPV − HNSCC. 2 These clinical differences may be related to the HPV effect on the immune system. 3The immune system plays an important role in HNSCC. The infiltration of T lymphocytes and their subsets in HNSCC has been extensively studied over recent years. However, B lymphocytes
Background Cellular communication is an essential feature of multicellular organisms. Binding of ligands to their homologous receptors, which activate specific cell signaling pathways, is a basic type of cellular communication and intimately linked to many degeneration processes leading to diseases. Main body This study reviewed the history of ligand-receptor and presents the databases which store ligand-receptor pairs. The recently applications and research tools of ligand-receptor interactions for cell communication at single cell level by using single cell RNA sequencing have been sorted out. Conclusion The summary of the advantages and disadvantages of analysis tools will greatly help researchers analyze cell communication at the single cell level. Learning cell communication based on ligand-receptor interactions by single cell RNA sequencing gives way to developing new target drugs and personalizing treatment.
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