Immune checkpoint pathways in immunotherapy for head and neck squamous cell carcinoma / 国际口腔科学杂志·英文版

With the understanding of the complex interaction between the tumour microenvironment and immunotherapy, there is increasing interest in the role of immune regulators in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of T cells and immune checkpoint molecules is important for the immune response to cancers. Immune checkpoint molecules include cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), T-cell immunoglobulin mucin protein 3 (TIM-3), lymphocyte activation gene 3 (LAG-3), T cell immunoglobin and immunoreceptor tyrosine-based inhibitory motif (TIGIT), glucocorticoid-induced tumour necrosis factor receptor (GITR) and V-domain Ig suppressor of T cell activation (VISTA). Many clinical trials using checkpoint inhibitors, as both monotherapies and combination therapies, have been initiated targeting these immune checkpoint molecules. This review summarizes the functional mechanism and use of various immune checkpoint molecules in HNSCC, including monotherapies and combination therapies, and provides better treatment options for patients with HNSCC.

Anti-cancer Effects of a Novel Quinoline Derivative 83b1 on Human Esophageal Squamous Cell Carcinoma through Down-Regulation of COX-2 mRNA and PGE₂ / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: 83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis. MATERIALS AND METHODS: A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2–derived prostaglandin E₂ (PGE₂) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively. In vivo anti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450. RESULTS: 83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPARδ), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2–derived PGE2 were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft. CONCLUSION: The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPARδ, and down-regulation of the cancer related genes and molecules.