Cutaneous malignant melanoma (hereafter called melanoma) is one of the most aggressive cancers with increasing incidence and mortality rates worldwide. In this study, we performed a systematic investigation of the tumor microenvironmental and genetic factors associated with melanoma to identify prognostic biomarkers for melanoma. We calculated the immune and stromal scores of melanoma patients from the Cancer Genome Atlas (TCGA) using the ESTIMATE algorithm and found that they were closely associated with patients' prognosis. Then the differentially expressed genes were obtained based on the immune and stromal scores, and prognostic immune-related genes further identified. Functional analysis and the protein-protein interaction network further revealed that these genes enriched in many immunerelated biological processes. In addition, the abundance of six infiltrating immune cells was analyzed using prognostic immune-related genes by TIMER algorithm. The unsupervised clustering analysis using immune-cell proportions revealed eight clusters with distinct survival patterns, suggesting that dendritic cells were most abundant in the microenvironment and CD8 + T cells and neutrophils were significantly related to patients' prognosis. Finally, we validated these genes in three independent cohorts from the Gene Expression Omnibus database. In conclusion, this study comprehensively analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for melanoma. K E Y W O R D S cutaneous melanoma, GEO, prognosis, TCGA, tumor microenvironment

Esophageal squamous cell cancer is a highly aggressive cancer with a dismal 5-year survival rate. CD47 is a cell transmembrane protein that is involved in cell apoptosis, proliferation, adhesion, migration, and antigen presentation in the immune system. By interacting with signal regulatory protein-α expressed in antigen-presenting cells (APCs), CD47 acts as an antiphagocytic mechanism to inhibit APC-dependent antigen presentation. Overexpression of CD47 was found in various types of cancer. However, its role in esophageal squamous cell cancer is not yet clear. Anti-CD47 is an antagonist of CD47 signaling pathways by competing with its ligand. In the current study, we investigated the effects of anti-CD47 treatment on the antitumor immune response in an esophageal squamous cell cancer preclinical model. We found that anti-CD47 treatment enhanced proinflammatory responses and increased CD8+ T-cell infiltration in tumor tissue in the animal model. T cells in anti-CD47-treated tumors showed higher PD-1 and CTLA-4 expression, indicating T-cell activation and the rationale of combining anti-CD47 with anti-PD-1 and CLTA-4. The combinatory treatment showed the best antitumor response, implying a novel treatment strategy. The effects of anti-CD47 depended on dendritic cell function. In patient samples, expression of CD47 was negatively correlated with CD8+ T-cell infiltration in esophageal squamous cell cancer patients. Taken together, CD47 might be a novel target to enhance anti-PD-1 and CLTA-4 efficacy in esophageal squamous cell cancer.

Objectives : keratin 16 (KRT16) is a type I cytokeratin that overexpressed in many kinds of cancers, but unlike other keratins, KRT16 was poorly studied, so the aim of current study was to determine the biological role of KRT16 in lung adenocarcinoma (LUAD). Materials and Methods : by utilizing open access data, we determined KRT16 expression in LUAD. After that we evaluated the biological role of KRT16 in-vitro and in-vivo . We also explored the reason for KRT16 overexpression. Last, we explored the clinical significance of KRT16 in LUAD. Results : we found KRT16 is overexpressed in LUAD and positively correlated with lymph node metastasis. Knockdown of KRT16 significantly influenced the LUAD cells' migration, invasion, proliferation and epithelial-mesenchymal transition (EMT). Moreover, TFAP2A could transcriptionally overexpress KRT16, which contributed to the TFAP2A tumorigenicity. Last, we determined that high level of KRT16 predicts poor prognosis of LUAD patients. Conclusions : our data indicate that, TFAP2A induced KRT16 overexpression promotes tumorigenicity in LUAD via EMT, and KRT16 expression could serve as an independent prognosis marker.